Moore, B. W. A soluble protein characteristic of the nervous system. Biochem. Biophys. Res. Commun. 19, 739–744 (1965).
Leclerc, E. & Heizmann, C. W. The importance of Ca2+/Zn2+ signaling S100 proteins and RAGE in translational medicine. Front. Biosci. (Schol. Ed.) 3, 1232–1262 (2011).
Hermann, A., Donato, R., Weiger, T. M. & Chazin, W. J. S100 calcium binding proteins and ion channels. Front. Pharmacol. 3, 67 (2012).
Donato, R. et al. Functions of S100 proteins. Curr. Mol. Med. 13, 24–57 (2013).
Yap, K. L., Ames, J. B., Swindells, M. B. & Ikura, M. Diversity of conformational states and changes within the EF-hand protein superfamily. Proteins 37, 499–507 (1999).
Zimmer, D. B. & Weber, D. J. The calcium-dependent interaction of S100B with its protein targets. Cardiovasc. Psychiatry Neurol. 2010, 728052 (2010).
von Bauer, R. et al. CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity. J. Immunol. 191, 369–377 (2013).
Dmytriyeva, O. et al. The metastasis-promoting S100A4 protein confers neuroprotection in brain injury. Nature Commun. 3, 1197 (2012).
Hibino, T. et al. S100A9 is a novel ligand of EMMPRIN that promotes melanoma metastasis. Cancer Res. 73, 172–183 (2013).
Hankins, J. L. et al. Ceramide-1-phosphate mediates endothelial cell invasion via the annexin a2/p11 heterotetrameric protein complex. J. Biol. Chem. 288, 19726–19738 (2013).
Zimmer, D. B., Eubanks, J. O., Ramakrishnan, D. & Criscitiello, M. F. Evolution of the S100 family of calcium sensor proteins. Cell Calcium 53, 170–179 (2012).
This reference clarifies inconsistencies regarding the S100 nomenclature and addresses species-specific differences in S100 protein expression that affect the translation of mouse studies to human disease.
Zimmer, D. B., Cornwall, E. H., Landar, A. & Song, W. The S100 protein family: history, function, and expression. Brain Res. Bull. 37, 417–429 (1995).
Henry, J. et al. Update on the epidermal differentiation complex. Front. Biosci. 17, 1517–1532 (2012).
Lunde, M. L. et al. Profiling of chromosomal changes in potentially malignant and malignant oral mucosal lesions from south and south-east Asia using array-comparative genomic hybridization. Cancer Genomics Proteomics 11, 127–140 (2014).
Chen, H. et al. Functional role of S100A14 genetic variants and their association with esophageal squamous cell carcinoma. Cancer Res. 69, 3451–3457 (2009).
Strazisar, M., Rott, T. & Glavac, D. Frequent polymorphic variations but rare tumour specific mutations of the S100A2 on 1q21 in non-small cell lung cancer. Lung Cancer 63, 354–359 (2009).
Isobe, T. et al. A rapid separation of S100 subunits by high performance liquid chromatography: the subunit compositions of S100 proteins. Biochem. Int. 6, 419–426 (1983).
Ichikawa, M., Williams, R., Wang, L., Vogl, T. & Srikrishna, G. S100A8/A9 activate key genes and pathways in colon tumor progression. Mol. Cancer Res. 9, 133–148 (2011).
Kallberg, E. et al. S100A9 interaction with TLR4 promotes tumor growth. PLoS ONE 7, e34207 (2012).
Berthier, S. et al. Molecular interface of S100A8 with cytochrome b558 and NADPH oxidase activation. PLoS ONE 7, e40277 (2012).
Wright, N. T. et al. Solution structure of S100A1 bound to the CapZ peptide (TRTK12). J. Mol. Biol. 386, 1265–1277 (2009).
Markowitz, J. et al. Calcium-binding properties of wild-type and EF-hand mutants of S100B in the presence and absence of a peptide derived from the C-terminal negative regulatory domain of p53. Biochemistry 44, 7305–7314 (2005).
Malashkevich, V. N. et al. Structure of Ca2+-bound S100A4 and its interaction with peptides derived from nonmuscle myosin-IIA. Biochemistry 47, 5111–5126 (2008).
Liriano, M. A. et al. Target binding to S100B reduces dynamic properties and increases Ca2+-binding affinity for wild type and EF-hand mutant proteins. J. Mol. Biol. 423, 365–385 (2012).
This reference discusses three models for the observed coupling between the binding of targets and calcium to S100 proteins, with a careful consideration of both the structural features and the dynamic properties of S100 proteins.
Ramagopal, U. A. et al. Structure of the S100A4/myosin-IIA complex. BMC Struct. Biol. 13, 31–46 (2013).
Orre, L. M., Pernemalm, M., Lengqvist, J., Lewensohn, R. & Lehtio, J. Up-regulation, modification, and translocation of S100A6 induced by exposure to ionizing radiation revealed by proteomics profiling. Mol. Cell Proteomics 6, 2122–2131 (2007).
Lim, S. Y., Raftery, M. J. & Geczy, C. L. Oxidative modifications of DAMPs suppress inflammation: the case for S100A8 and S100A9. Antioxid. Redox Signal. 15, 2235–2248 (2011).
Bowers, R. R., Manevich, Y., Townsend, D. M. & Tew, K. D. Sulfiredoxin redox-sensitive interaction with S100A4 and non-muscle myosin IIA regulates cancer cell motility. Biochemistry 51, 7740–7754 (2012).
Miranda, K. J., Loeser, R. F. & Yammani, R. R. Sumoylation and nuclear translocation of S100A4 regulates IL-11β mediated production of matrix metalloprotinase-13. J. Biol. Chem. 285, 31517–31524 (2010).
Wang, H. et al. S100B promotes glioma growth through chemoattraction of myeloid-derived macrophages. Clin. Cancer Res. 19, 3764–3775 (2013).
Koboldt, D. C. et al. Comprehensive molecular portraits of human breast tumours. Nature 490, 61–70 (2012).
Hunter, K. D., Parkinson, E. K. & Harrison, P. R. Profiling early head and neck cancer. Nature Rev. Cancer 5, 127–135 (2005).
Barbieri, C. E., Demichelis, F. & Rubin, M. A. Molecular genetics of prostate cancer: emerging appreciation of genetic complexity. Histopathology 60, 187–198 (2012).
Flaherty, K. T., Hodi, F. S. & Fisher, D. E. From genes to drugs: targeted strategies for melanoma. Nature Rev. Cancer 12, 349–361 (2012).
Sadanandam, A. et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nature Med. 19, 619–625 (2013).
Legolvan, M. P., Taliano, R. J. & Resnick, M. B. Application of molecular techniques in the diagnosis, prognosis and management of patients with colorectal cancer: a practical approach. Hum. Pathol. 43, 1157–1168 (2012).
Hao, J. et al. Selective expression of S100A11 in lung cancer and its role in regulating proliferation of adenocarcinomas cells. Mol. Cell Biochem. 359, 323–332 (2012).
Zhou, G. et al. Reciprocal negative regulation between S100A7/psoriasin and β-catenin signaling plays an important role in tumor progression of squamous cell carcinoma of oral cavity. Oncogene 27, 3527–3538 (2008).
Wolf, R., Ruzicka, T. & Yuspa, S. H. Novel S100A7 (psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function. Amino Acids 41, 789–796 (2011).
Heizmann, C. W. S100B protein in clinical diagnostics: assay specificity. Clin. Chem. 50, 249–251 (2004).
Horiuchi, A. et al. Hypoxia upregulates ovarian cancer invasiveness via the binding of HIF-1α to a hypoxia-induced, methylation free hypoxia response element (HRE) of S100A4 gene. Int. J. Cancer 131, 1755–1767 (2012).
Lesniak, W. Epigenetic regulation of S100 protein expression. Clin. Epigenetics 2, 77–83 (2011).
Gibadulinova, A., Tothova, V., Pastorek, J. & Pastorekova, S. Transcriptional regulation and functional implication of S100P in cancer. Amino Acids 41, 885–892 (2011).
Wang, Q. et al. S100P, a potential novel prognostic marker in colorectal cancer. Oncol. Rep. 28, 303–310 (2012).
Day, T. & Bianco-Miotto, T. Common gene pathways and families altered by DNA methylation in breast and prostate cancer. Endocr. Relat. Cancer 20, R215–R232 (2013).
Guo, C. et al. Global identification of MLL2-targeted loci reveals MLL2's role in diverse signaling pathways. Proc. Natl Acad. Sci. USA 109, 17603–17608 (2012).
Sack, U. & Stein, U. Wnt up your mind — intervention strategies for S100A4-induced metastasis in colon cancer. Gen. Physiol. Biophys. 28, F55–F64 (2009).
Chandramouli, A. et al. The induction of S100P expression by the prostaglandin E (PGE)/EP4 receptor signaling pathway in colon cancer cells. Cancer Biol. Ther. 10, 1056–1066 (2010).
Grebhardt, S., Veltkamp, C., Strobel, P. & Mayer, D. Hypoxia and HIF-1 increase S100A8 and S100A9 expression in prostate cancer. Int. J. Cancer 131, 2785–2794 (2012).
Miao, L. et al. Prostaglandin E2 stimulates S100A8 expression by activating protein kinase A and CCAAT/enhancer-binding-protein-beta in prostate cancer cells. Int. J. Biochem. Cell Biol. 44, 1919–1928 (2012).
Nemeth, J. et al. S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis. Hepatology 50, 1251–1262 (2009).
Lee, Y. M., Kim, Y. K., Eun, H. C. & Chung, J. H. Changes in S100A8 expression in UV-irradiated and aged human skin in vivo. Arch. Dermatol. Res. 301, 523–529 (2009).
Gebhardt, C. et al. RAGE signaling sustains inflammation and promotes tumor development. J. Exp. Med. 205, 275–285 (2008).
Deol, Y. S., Nasser, M. W., Yu, L., Zou, X. & Ganju, R. K. Tumor-suppressive effects of psoriasin (S100A7) are mediated through the β-catenin/T cell factor 4 protein pathway in estrogen receptor-positive breast cancer cells. J. Biol. Chem. 286, 44845–44854 (2011).
Gross, S. R., Sin, C. G., Barraclough, R. & Rudland, P. S. Joining S100 proteins and migration: for better or for worse, in sickness and in health. Cell. Mol. Life Sci. 71, 1551–1579 (2013).
Leclerc, E., Heizmann, C. W. & Vetter, S. W. RAGE and S100 protein transcription levels are highly variable in human melanoma tumors and cells. Gen. Physiol. Biophys. 28, F65–F75 (2009).
Nikitenko, L. L., Lloyd, B. H., Rudland, P. S., Fear, S. & Barraclough, R. Localisation by in situ hybridisation of S100A4 (p9Ka) mRNA in primary human breast tumour specimens. Int. J. Cancer 86, 219–228 (2000).
Lee, W. Y. et al. Expression of S100A4 and Met: potential predictors for metastasis and survival in early-stage breast cancer. Oncology 66, 429–438 (2004).
de Silva Rudland, S. et al. Association of S100A4 and osteopontin with specific prognostic factors and survival of patients with minimally invasive breast cancer. Clin. Cancer Res. 12, 1192–1200 (2006).
Cross, S. S., Hamdy, F. C., Deloulme, J. C. & Rehman, I. Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers. Histopathology 46, 256–269 (2005).
Al-Haddad, S. et al. Psoriasin (S100A7) expression and invasive breast cancer. Am. J. Pathol. 155, 2057–2066 (1999).
Emberley, E. D., Alowami, S., Snell, L., Murphy, L. C. & Watson, P. H. S100A7 (psoriasin) expression is associated with aggressive features and alteration of Jab1 in ductal carcinoma in situ of the breast. Breast Cancer Res. 6, R308–R315 (2004).
Arai, K. et al. S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast. Curr. Cancer Drug Targets 8, 243–252 (2008).
McKiernan, E., McDermott, E. W., Evoy, D., Crown, J. & Duffy, M. J. The role of S100 genes in breast cancer progression. Tumour Biol. 32, 441–450 (2011).
Schor, A. P., Carvalho, F. M., Kemp, C., Silva, I. D. & Russo, J. S100P calcium-binding protein expression is associated with high-risk proliferative lesions of the breast. Oncol. Rep. 15, 3–6 (2006).
Emberley, E. D., Murphy, L. C. & Watson, P. H. S100A7 and the progression of breast cancer. Breast Cancer Res. 6, 153–159 (2004).
Emberley, E. D. et al. Psoriasin (S100A7) expression is associated with poor outcome in estrogen receptor-negative invasive breast cancer. Clin. Cancer Res. 9, 2627–2631 (2003).
Emberley, E. D. et al. The S100A7–c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer. Cancer Res. 65, 5696–5702 (2005).
Nasser, M. W. et al. S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways. Cancer Res. 72, 604–615 (2012).
Emberley, E. D. et al. Psoriasin interacts with Jab1 and influences breast cancer progression. Cancer Res. 63, 1954–1961 (2003).
Krop, I. et al. A putative role for psoriasin in breast tumor progression. Cancer Res. 65, 11326–11334 (2005).
Paruchuri, V. et al. S100A7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formation. PLoS ONE 3, e1741 (2008).
Sneh, A. et al. Differential role of psoriasin (S100A7) in estrogen receptor α positive and negative breast cancer cells occur through actin remodeling. Breast Cancer Res. Treat. 138, 727–739 (2013).
Enerback, C. et al. Psoriasin expression in mammary epithelial cells in vitro and in vivo. Cancer Res. 62, 43–47 (2002).
Shubbar, E., Vegfors, J., Carlstrom, M., Petersson, S. & Enerback, C. Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation. Breast Cancer Res. Treat. 134, 71–80 (2012).
Rudland, P. S. et al. Prognostic significance of the metastasis-inducing protein S100A4 (p9Ka) in human breast cancer. Cancer Res. 60, 1595–1603 (2000).
Davies, B. R., Davies, M. P., Gibbs, F. E., Barraclough, R. & Rudland, P. S. Induction of the metastatic phenotype by transfection of a benign rat mammary epithelial cell line with the gene for p9Ka, a rat calcium-binding protein, but not with the oncogene EJ-ras-1. Oncogene 8, 999–1008 (1993).
Ambartsumian, N. S. et al. Metastasis of mammary carcinomas in GRS/A hybrid mice transgenic for the mts1 gene. Oncogene 13, 1621–1630 (1996).
Davies, M. P. et al. Expression of the calcium-binding protein S100A4 (p9Ka) in MMTV-neu transgenic mice induces metastasis of mammary tumours. Oncogene 13, 1631–1637 (1996).
Using murine models of breast cancer, references 77, 78 and 79 established S100A4 as a mediator of tumour metastasis.
Kim, E. J. & Helfman, D. M. Characterization of the metastasis-associated protein, S100A4. Roles of calcium binding and dimerization in cellular localization and interaction with myosin. J. Biol. Chem. 278, 30063–30073 (2003).
Wang, Y. et al. Profiling signaling polarity in chemotactic cells. Proc. Natl Acad. Sci. USA 104, 8328–8333 (2007).
House, R. P., Garrett, S. C. & Bresnick, A. R. in Signaling Pathways and Molecular Mediators in Metastasis (ed. Fatatis, A.) 91–113 (Springer Netherlands, 2012).
Kriajevska, M. V. et al. Non-muscle myosin heavy chain as a possible target for protein encoded by metastasis-related mts-1 gene. J. Biol. Chem. 269, 19679–19682 (1994).
Ford, H. L., Silver, D. L., Kachar, B., Sellers, J. R. & Zain, S. B. Effect of Mts1 on the structure and activity of nonmuscle myosin II. Biochemistry 36, 16321–16327 (1997).
Li, Z. H., Dulyaninova, N. G., House, R. P., Almo, S. C. & Bresnick, A. R. S100A4 regulates macrophage chemotaxis. Mol. Biol. Cell 21, 2598–2610 (2010).
Chen, M., Bresnick, A. R. & O'Connor, K. L. Coupling S100A4 to rhotekin alters Rho signaling output in breast cancer cells. Oncogene 32, 3754–3764 (2012).
O'Connell, J. T. et al. VEGF-A and Tenascin-C produced by S100A4+ stromal cells are important for metastatic colonization. Proc. Natl Acad. Sci. USA 108, 16002–16007 (2011).
Xue, C., Plieth, D., Venkov, C., Xu, C. & Neilson, E. G. The gatekeeper effect of epithelial–mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Res. 63, 3386–3394 (2003).
Grum-Schwensen, B. et al. Lung metastasis fails in MMTV-PyMT oncomice lacking S100A4 due to a T-cell deficiency in primary tumors. Cancer Res. 70, 936–947 (2010).
Kidd, S. et al. Origins of the tumor microenvironment: quantitative assessment of adipose-derived and bone marrow-derived stroma. PLoS ONE 7, e30563 (2012).
Cabezon, T. et al. Expression of S100A4 by a variety of cell types present in the tumor microenvironment of human breast cancer. Int. J. Cancer 121, 1433–1444 (2007).
Forst, B. et al. Metastasis-inducing S100A4 and RANTES cooperate in promoting tumor progression in mice. PLoS ONE 5, e10374 (2010).
Klingelhofer, J. et al. Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion. Neoplasia 14, 1260–1268 (2012).
Hernandez, J. L. et al. Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody. PLoS ONE 8, e72480 (2013).
Ambartsumian, N. et al. The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor. Oncogene 20, 4685–4695 (2001).
Schmidt-Hansen, B. et al. Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity. Oncogene 23, 5487–5495 (2004).
Bettum, I. J. et al. Metastasis-associated protein S100A4 induces a network of inflammatory cytokines that activate stromal cells to acquire pro-tumorigenic properties. Cancer Lett. 344, 28–39 (2014).
Hansen, M. T. et al. A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4. Oncogene http://dx.doi.org/10.1038/onc.2013.568 (2014).
Goncalves, A. et al. Protein profiling of human breast tumor cells identifies novel biomarkers associated with molecular subtypes. Mol. Cell Proteomics 7, 1420–1433 (2008).
Cheng, P. et al. Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J. Exp. Med. 205, 2235–2249 (2008).
Acharyya, S. et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell 150, 165–178 (2012).
Sinha, P. et al. Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J. Immunol. 181, 4666–4675 (2008).
Yin, C. et al. RAGE-binding S100A8/A9 promotes the migration and invasion of human breast cancer cells through actin polymerization and epithelial–mesenchymal transition. Breast Cancer Res. Treat. 142, 297–309 (2013).
Siegenthaler, G. et al. A heterocomplex formed by the calcium-binding proteins MRP8 (S100A8) and MRP14 (S100A9) binds unsaturated fatty acids with high affinity. J. Biol. Chem. 272, 9371–9377 (1997).
Markowitz, J. & Carson, W. E. 3rd. Review of S100A9 biology and its role in cancer. Biochim. Biophys. Acta 1835, 100–109 (2012).
Gomes, L. H. et al. S100A8 and S100A9—oxidant scavengers in inflammation. Free Radic. Biol. Med. 58, 170–186 (2012).
Hiratsuka, S., Watanabe, A., Aburatani, H. & Maru, Y. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nature Cell Biol. 8, 1369–1375 (2006).
Hiratsuka, S. et al. The S100A8–serum amyloid A3–TLR4 paracrine cascade establishes a pre-metastatic phase. Nature Cell Biol. 10, 1349–1355 (2008).
References 107 and 108 demonstrate that tumour-derived factors induce S100A8 and/or S100A9 expression in the lung to establish a pre-metastatic niche and create a permissive environment for pulmonary metastasis.
Liu, Y. et al. Premetastatic soil and prevention of breast cancer brain metastasis. Neuro Oncol. 15, 891–903 (2013).
Zimmer, D. B., Chaplin, J., Baldwin, A. & Rast, M. S100-mediated signal transduction in the nervous system and neurological diseases. Cell. Mol. Biol. (Noisy-le-Grand) 51, 201–214 (2005).
Nonaka, D., Chiriboga, L. & Rubin, B. P. Differential expression of S100 protein subtypes in malignant melanoma, and benign and malignant peripheral nerve sheath tumors. J. Cutan. Pathol. 35, 1014–1019 (2008).
Maelandsmo, G. M. et al. Differential expression patterns of S100A2, S100A4 and S100A6 during progression of human malignant melanoma. Int. J. Cancer 74, 464–469 (1997).
Petersson, S., Shubbar, E., Enerback, L. & Enerback, C. Expression patterns of S100 proteins in melanocytes and melanocytic lesions. Melanoma Res. 19, 215–225 (2009).
Brouard, M. C., Saurat, J. H., Ghanem, G. & Siegenthaler, G. Urinary excretion of epidermal-type fatty acid-binding protein and S100A7 protein in patients with cutaneous melanoma. Melanoma Res. 12, 627–631 (2002).
Hensler, S. & Mueller, M. M. Inflammation and skin cancer: old pals telling new stories. Cancer J. 19, 517–524 (2013).
Roltsch, E., Holcomb, L., Young, K. A., Marks, A. & Zimmer, D. B. PSAPP mice exhibit regionally selective reductions in gliosis and plaque deposition in response to S100B ablation. J. Neuroinflammation 7, 78 (2010).
Peinado, H. et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nature Med. 18, 883–891 (2012).
Geara, F. B. & Ang, K. K. Radiation therapy for malignant melanoma. Surg. Clin. North Am. 76, 1383–1398 (1996).
Satyamoorthy, K. et al. Aberrant regulation and function of wild-type p53 in radioresistant melanoma cells. Cell Growth Differ. 11, 467–474 (2000).
Sawa, H. et al. Histone deacetylase inhibitors such as sodium butyrate and trichostatin A induce apoptosis through an increase of the bcl-2-related protein Bad. Brain Tumor Pathol. 18, 109–114 (2001).
Lin, J. et al. Inhibiting S100B restores p53 levels in primary malignant melanoma cancer cells. J. Biol. Chem. 279, 34071–34077 (2004).
Lin, J. et al. Inhibition of p53 transcriptional activity by the S100B calcium-binding protein. J. Biol. Chem. 276, 35037–35041 (2001).
Zimmer, D. B., Lapidus, R. G. & Weber, D. J. In vivo screening of S100B inhibitors for melanoma therapy. Methods Mol. Biol. 963, 303–317 (2013).
Hartman, K. G. et al. Complex formation between S100B and the p90 ribosomal S6 kinase (RSK) in malignant melanoma is Ca2+-dependent and inhibits ERK-mediated phosphorylation of RSK. J. Biol. Chem. 289, 12886–12895 (2014).
Lin, J., Yang, Q., Wilder, P. T., Carrier, F. & Weber, D. J. The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma. J. Biol. Chem. 285, 27487–27498 (2010).
References 121, 122 and 125 establish the molecular basis of S100B-mediated regulation of p53 in melanoma, thus informing the development of S100B inhibitors.
Baudier, J., Delphin, C., Grunwald, D., Khochbin, S. & Lawrence, J. J. Characterization of the tumor suppressor protein p53 as a protein kinase C substrate and a S100b-binding protein. Proc. Natl Acad. Sci. USA 89, 11627–11631 (1992).
Wilder, P. T. et al. Recognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B. Biochim. Biophys. Acta 1763, 1284–1297 (2006).
Smith, J. et al. The effect of pentamidine on melanoma ex vivo. Anticancer Drugs 21, 181–185 (2010).
Hammacher, A., Thompson, E. W. & Williams, E. D. Interleukin-6 is a potent inducer of S100P, which is up-regulated in androgen-refractory and metastatic prostate cancer. Int. J. Biochem. Cell Biol. 37, 442–450 (2005).
Tothova, V. et al. Glucocorticoid receptor-mediated transcriptional activation of S100P gene coding for cancer-related calcium-binding protein. J. Cell Biochem. 112, 3373–3384 (2011).
Barry, S. et al. S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells. Clin. Exp. Metastasis 30, 251–264 (2013).
Bulk, E. et al. Adjuvant therapy with small hairpin RNA interference prevents non-small cell lung cancer metastasis development in mice. Cancer Res. 68, 1896–1904 (2008).
Ding, Q. et al. APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis. J. Clin. Invest. 121, 4526–4536 (2011).
Jiang, L. et al. Targeting S100P inhibits colon cancer growth and metastasis by lentivirus-mediated RNA interference and proteomic analysis. Mol. Med. 17, 709–716 (2011).
Austermann, J., Nazmi, A. R., Muller-Tidow, C. & Gerke, V. Characterization of the Ca2+ -regulated ezrin–S100P interaction and its role in tumor cell migration. J. Biol. Chem. 283, 29331–29340 (2008).
Heil, A. et al. S100P is a novel interaction partner and regulator of IQGAP1. J. Biol. Chem. 286, 7227–7238 (2011).
Arumugam, T., Simeone, D. M., Schmidt, A. M. & Logsdon, C. D. S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). J. Biol. Chem. 279, 5059–5065 (2004).
Afanador, L. et al. The Ca2+ sensor S100A1 modulates neuroinflammation, histopathology and Akt activity in the PSAPP Alzheimer's disease mouse model. Cell Calcium 56, 68–80 (2014).
Rohde, D. et al. S100A1: a multifaceted therapeutic target in cardiovascular disease. J. Cardiovasc. Transl. Res. 3, 525–537 (2010).
Sack, U. et al. S100A4-induced cell motility and metastasis is restricted by the Wnt/β-catenin pathway inhibitor calcimycin in colon cancer cells. Mol. Biol. Cell 22, 3344–3354 (2011).
Stein, U. et al. Intervening in β-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis. Neoplasia 13, 131–144 (2011).
Weber, C. et al. Therapeutic safety of high myocardial expression levels of the molecular inotrope S100A1 in a preclinical heart failure model. Gene Ther. 21, 131–138 (2014).
Dakhel, S. et al. S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer. Oncogenesis 3, e92 (2014).
Qin, H. et al. Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice. Nature Med. 20, 676–681 (2014).
This reference uses an innovative and unbiased approach to identify novel diagnostic and therapeutic targets on the surface of MDSCs, which were subsequently determined to be S100 proteins.
Dhar, A. et al. Simultaneous inhibition of key growth pathways in melanoma cells and tumor regression by a designed bidentate constrained helical peptide. Biopolymers 101, 344–358 (2014).
Bjork, P. et al. Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides. PLoS Biol. 7, e97 (2009).
Pili, R. et al. Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. J. Clin. Oncol. 29, 4022–4028 (2011).
Jennbacken, K. et al. Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline-3-carboxamide tasquinimod (ABR-215050). Prostate 72, 913–924 (2011).
Arumugam, T., Ramachandran, V., Maxwell, D., Bornmann, W. G. & Logsdon, C. D. Designing and developing S100P inhibitor 5-methyl cromolyn (C5OH) for pancreatic cancer therapy. Mol. Cancer Ther. 12, 654–662 (2013).
Kim, C. E., Lim, S. K. & Kim, J. S. In vivo antitumor effect of cromolyn in PEGylated liposomes for pancreatic cancer. J. Control. Release 157, 190–195 (2012).
Mack, G. S. & Marshall, A. Lost in migration. Nature Biotech. 28, 214–229 (2010).
Rani, S. G., Mohan, S. K. & Yu, C. Molecular level interactions of S100A13 with amlexanox: inhibitor for formation of the multiprotein complex in the nonclassical pathway of acidic fibroblast growth factor. Biochemistry 49, 2585–2592 (2010).
Okada, M., Tokumitsu, H., Kubota, Y. & Kobayashi, R. Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein. Biochem. Biophys. Res. Commun. 292, 1023–1030 (2002).
Malashkevich, V. N. et al. Phenothiazines inhibit S100A4 function by inducing protein oligomerization. Proc. Natl Acad. Sci. USA 107, 8605–8610 (2010).
Garrett, S. C. et al. A biosensor of S100A4 metastasis factor activation: inhibitor screening and cellular activation dynamics. Biochemistry 47, 986–996 (2008).
Bjork, P. et al. Common interactions between S100A4 and S100A9 defined by a novel chemical probe. PLoS ONE 8, e63012 (2013).
Dulyaninova, N. G. et al. Cysteine 81 is critical for the interaction of S100A4 and myosin-IIA. Biochemistry 50, 7218–7227 (2011).
Reddy, T. R., Li, C., Fischer, P. M. & Dekker, L. V. Three-dimensional pharmacophore design and biochemical screening identifies substituted 1,2,4-triazoles as inhibitors of the annexin A2-S100A10 protein interaction. ChemMedChem 7, 1435–1446 (2012).
Yoshimura, C., Miyafusa, T. & Tsumoto, K. Identification of small-molecule inhibitors of the human S100B–p53 interaction and evaluation of their activity in human melanoma cells. Bioorg. Med. Chem. 21, 1109–1115 (2013).
Cavalier, M. C. et al. Covalent small molecule inhibitors of Ca2+-bound S100B. Biochemistry 53, 6628–6640 (2014).
Using different approaches, references 152, 154 and 160 identify small-molecule inhibitors of S100 proteins and demonstrate the multiple mechanisms for disrupting S100–target interactions.
Agamennone, M. et al. Fragmenting the S100B–p53 interaction: combined virtual/biophysical screening approaches to identify ligands. ChemMedChem 5, 428–435 (2010).
Charpentier, T. H. et al. Divalent metal ion complexes of S100B in the absence and presence of pentamidine. J. Mol. Biol. 382, 56–73 (2008).
Markowitz, J. et al. Identification and characterization of small molecule inhibitors of the calcium-dependent S100B–p53 tumor suppressor interaction. J. Med. Chem. 47, 5085–5093 (2004).
Wright, P. E. & Dyson, H. J. Linking folding and binding. Curr. Opin. Struct. Biol. 19, 31–38 (2009).
Marlow, M. S., Dogan, J., Frederick, K. K., Valentine, K. G. & Wand, A. J. The role of conformational entropy in molecular recognition by calmodulin. Nature Chem. Biol. 6, 352–358 (2010).
Tsai, C. J., Ma, B. & Nussinov, R. Folding and binding cascades: shifts in energy landscapes. Proc. Natl Acad. Sci. USA 96, 9970–9972 (1999).
Markowitz, J. et al. Design of inhibitors for S100B. Curr. Top. Med. Chem. 5, 1093–1108 (2005).
Wang, G. et al. Mutually antagonistic actions of S100A4 and S100A1 on normal and metastatic phenotypes. Oncogene 24, 1445–1454 (2005).
Grigorian, M. et al. Effect of mts1 (S100A4) expression on the progression of human breast cancer cells. Int. J. Cancer 67, 831–841 (1996).
Lloyd, B. H., Platt-Higgins, A., Rudland, P. S. & Barraclough, R. Human S100A4 (p9Ka) induces the metastatic phenotype upon benign tumour cells. Oncogene 17, 465–473 (1998).
Fujiwara, M. et al. Stable knockdown of S100A4 suppresses cell migration and metastasis of osteosarcoma. Tumour Biol. 32, 611–622 (2011).
Maelandsmo, G. M. et al. Reversal of the in vivo metastatic phenotype of human tumor cells by an anti-CAPL (mts1) ribozyme. Cancer Res. 56, 5490–5498 (1996).
Zhang, G., Li, M., Jin, J., Bai, Y. & Yang, C. Knockdown of S100A4 decreases tumorigenesis and metastasis in osteosarcoma cells by repression of matrix metalloproteinase-9. Asian Pac. J. Cancer Prev. 12, 2075–2080 (2011).
Tsai, W. C., Tsai, S. T., Jin, Y. T. & Wu, L. W. Cyclooxygenase-2 is involved in S100A2-mediated tumor suppression in squamous cell carcinoma. Mol. Cancer Res. 4, 539–547 (2006).
Lo, J. F. et al. The epithelial–mesenchymal transition mediator S100A4 maintains cancer-initiating cells in head and neck cancers. Cancer Res. 71, 1912–1923 (2011).
Rasanen, K. et al. Comparative secretome analysis of epithelial and mesenchymal subpopulations of head and neck squamous cell carcinoma identifies S100A4 as a potential therapeutic target. Mol. Cell Proteomics 12, 3778–3792 (2013).
Chen, D. et al. S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells. World J. Gastroenterol. 18, 915–922 (2012).
Bulk, E. et al. S100A2 induces metastasis in non-small cell lung cancer. Clin. Cancer Res. 15, 22–29 (2009).
Takenaga, K., Nakamura, Y. & Sakiyama, S. Expression of antisense RNA to S100A4 gene encoding an S100-related calcium-binding protein suppresses metastatic potential of high-metastatic Lewis lung carcinoma cells. Oncogene 14, 331–337 (1997).
Ortiz, M. L., Lu, L., Ramachandran, I. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the development of lung cancer. Cancer Immunol. Res. 2, 50–58 (2014).
Phipps, K. D., Surette, A. P., O'Connell, P. A. & Waisman, D. M. Plasminogen receptor S100A10 is essential for the migration of tumor-promoting macrophages into tumor sites. Cancer Res. 71, 6676–6683 (2011).
Kang, M. et al. S100A3 suppression inhibits in vitro and in vivo tumor growth and invasion of human castration-resistant prostate cancer cells. Urology http://dx.doi.org/10.1016/j.urology.2014.09.018 (2014).
Siddique, H. R. et al. The S100A4 oncoprotein promotes prostate tumorigenesis in a transgenic mouse model: regulating NFκB through the RAGE receptor. Genes Cancer 4, 224–234 (2013).
Saleem, M. et al. S100A4 accelerates tumorigenesis and invasion of human prostate cancer through the transcriptional regulation of matrix metalloproteinase 9. Proc. Natl Acad. Sci. USA 103, 14825–14830 (2006).
Ochiya, T., Takenaga, K. & Endo, H. Silencing of S100A4, a metastasis-associated protein, in endothelial cells inhibits tumor angiogenesis and growth. Angiogenesis 17, 17–26 (2013).
Grebhardt, S., Muller-Decker, K., Bestvater, F., Hershfinkel, M. & Mayer, D. Impact of S100A8/A9 expression on prostate cancer progression in vitro and in vivo. J. Cell. Physiol. 229, 661–671 (2013).
Basu, G. D. et al. Functional evidence implicating S100P in prostate cancer progression. Int. J. Cancer 123, 330–339 (2008).
Dahlmann, M. et al. Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation. Oncotarget 3, 783–797 (2012).
Takenaga, K. et al. Modified expression of Mts1/S100A4 protein in C6 glioma cells or surrounding astrocytes affects migration of tumor cells in vitro and in vivo. Neurobiol. Dis. 25, 455–463 (2007).
Chen, S. et al. Comparative proteomics of glioma stem cells and differentiated tumor cells identifies S100A9 as a potential therapeutic target. J. Cell Biochem. 114, 2795–2808 (2013).
Hua, J. et al. Short hairpin RNA-mediated inhibition of S100A4 promotes apoptosis and suppresses proliferation of BGC823 gastric cancer cells in vitro and in vivo. Cancer Lett. 292, 41–47 (2010).
Zhang, J., Zhang, K. & Jiang, X. S100A6 as a potential serum prognostic biomarker and therapeutic target in gastric cancer. Dig. Dis. Sci. 59, 2136–2144 (2014).
Levett, D. et al. Transfection of S100A4 produces metastatic variants of an orthotopic model of bladder cancer. Am. J. Pathol. 160, 693–700 (2002).
Arumugam, T., Ramachandran, V. & Logsdon, C. D. Effect of cromolyn on S100P interactions with RAGE and pancreatic cancer growth and invasion in mouse models. J. Natl Cancer Inst. 98, 1806–1818 (2006).
Yang, X. C. et al. RNA interference suppression of A100A4 reduces the growth and metastatic phenotype of human renal cancer cells via NF-κB-dependent MMP-2 and bcl-2 pathway. Eur. Rev. Med. Pharmacol. Sci. 17, 1669–1680 (2013).
Zhao, F. T., Jia, Z. S., Yang, Q., Song, L. & Jiang, X. J. S100A14 promotes the growth and metastasis of hepatocellular carcinoma. Asian Pac. J. Cancer Prev. 14, 3831–3836 (2013).
Shi, Y. et al. Ribonucleic acid interference targeting S100A4 (Mts1) suppresses tumor growth and metastasis of anaplastic thyroid carcinoma in a mouse model. J. Clin. Endocrinol. Metab. 91, 2373–2379 (2006).
Reeb, A. N. et al. S100A8 is a novel therapeutic target for anaplastic thyroid carcinoma. J. Clin. Endocrinol. Metab. http://dx.doi.org/10.1210/jc.2014-2988 (2014).
Anania, M. C. et al. S100A11 overexpression contributes to the malignant phenotype of papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 98, E1591–E1600 (2013).