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  • Original Article
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CAPC negatively regulates NF-κB activation and suppresses tumor growth and metastasis

Abstract

CAPC, also known as LRRC26, is expressed in normal prostate and salivary gland. We developed a mAb to CAPC and used it to characterize the protein and study its function. CAPC protein was detected in normal prostate and salivary gland, in several human breast cancer cell lines and in the prostate cancer cell line LNCaP. Knockdown of CAPC by siRNA in LNCaP cells enhanced anchorage-independent growth in soft agar. Conversely, overexpression of CAPC in MDA-231 breast cancer cells and A431 epidermoid cancer cells inhibited growth in soft agar and tumorigenesis in nude mice, and suppressed the metastasis of MDA-231 cells to the lung. Overexpression of CAPC downregulated NF-κB activity and its target genes, including GM-CSF (CSF2), CXCL1, IL8 and LTB1. It also suppressed genes encoding the serine protease mesotrypsin (PRSS3) and cystatin SN (CST1). CAPC expressing tumors showed a decrease in the number of proliferating cells and a large increase in ECM. The role of CAPC in the suppression of tumor growth and metastasis may be through its alteration of the tumor microenvironment.

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References

  • American Cancer Society (2009). Cancer Facts and Figures, 2009. American Cancer Society: Atlanta, GA.

  • Apte RN, Dolan S, Elkabets M, White MR, Reich E, Carmi Y et al. (2006). The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor–host interactions. Cancer Metastasis Rev 25: 387–408.

    Article  CAS  PubMed  Google Scholar 

  • Basbaum CB, Werb Z . (1996). Focalized proteolysis: spatial and temporal regulation of extracellular matrix degradation at the cell surface. Curr Opin Cell Biol 8: 731–738.

    Article  CAS  PubMed  Google Scholar 

  • Chatterjee SK, Zetter BR . (2005). Cancer biomarkers: knowing the present and predicting the future. Future Oncol 1: 37–50.

    Article  CAS  PubMed  Google Scholar 

  • Choi EH, Kim JT, Kim JH, Kim SY, Song EY, Kim JW et al. (2009). Upregulation of the cysteine protease inhibitor, cystatin SN, contributes to cell proliferation and cathepsin inhibition in gastric cancer. Clin Chim Acta 406: 45–51.

    Article  CAS  PubMed  Google Scholar 

  • Dixit V, Mak TW . (2002). NF-κB signaling: many roads lead to Madrid. Cell 111: 615–619.

    Article  CAS  PubMed  Google Scholar 

  • Egland KA, Vincent JJ, Strausberg R, Lee B, Pastan I . (2003). Discovery of the breast cancer gene BASE using a molecular approach to enrich genes encoding membrane and secreted proteins. Proc Natl Acad Sci U S A 100: 1099–1104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egland K, Liu XF, Squires S, Nagata S, Man YG, Bera TK et al. (2006). High expression of a cytokeratin-associated protein in many cancers. Proc Natl Acad Sci USA 103: 5929–5934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friedi P, Wolk K . (2008). Tube travel: the role of proteases in individual and collective cancer cell invasion. Cancer Res 68: 7247–7249.

    Article  Google Scholar 

  • Hockla A, Radisky DC, Radisky ES . (2010). Mesotrypsin promotes malignant growth of breast cancer cells through shedding of CD109. Breast Cancer Res Treat 124: 27–38.

    Article  CAS  PubMed  Google Scholar 

  • Joyce JA, Pollard JW . (2009). Microenvironmental regulation of metastasis. Nat Rev Cancer 9: 239–252.

    Article  CAS  PubMed  Google Scholar 

  • Karin M, Greten FR . (2005). NF-κB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5: 749–759.

    Article  CAS  PubMed  Google Scholar 

  • Lee CH, Jeon YT, Kim SH, Song YS . (2007). NF-κB as a potential molecular target for cancer therapy. Biofactors 29: 19–35.

    Article  CAS  PubMed  Google Scholar 

  • Lee M, Fridman R, Mobashery S . (2004). Extracellular proteases as targets for treatment of cancer metastases. Chem Soc Rev 10: 401–409.

    Article  Google Scholar 

  • Li F, Sethi G . (2010). Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. Biochim Biophys Acta 1805: 167–180.

    CAS  PubMed  Google Scholar 

  • Loza MJ, McCall CE, Li L, Isaacs WB, Xu J et al. (2007). Assembly of inflammation-related genes for pathway-focused genetic analysis. PLoS One 2: e1035.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nam JS, Kang MJ, Suchar AM, Shimamura T, Kohn EA, Michalowska AM et al. (2006). Chemokine (C-C motif) ligand 2 mediates the prometastatic effect of dysadherin in human breast cancer cells. Cancer Res 66: 7176–7184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naugler WE, Karin M . (2008). NF-κB and cancer-identifying targets and mechanisms. Curr Opin Genet Dev 18: 19–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pacifico F, Leonardi A . (2006). NF-κB in solid tumors. Biochem Pharmacol 72: 1142–1152.

    Article  CAS  PubMed  Google Scholar 

  • Park BK, Zhang H, Zeng Q, Dai J, Keller ET, Giordano T et al. (2007). NF-κB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF. Nat Med 13: 62–69.

    Article  CAS  PubMed  Google Scholar 

  • Porta C, Larghi P, Rimoldi M, Totaro MG, Allavena P, Mantovani A et al. (2009). Cellular and molecular pathways linking inflammation and cancer. Immunology 214: 761–777.

    CAS  Google Scholar 

  • Raman D, Baugher PJ, Thu YM, Richmond A . (2007). Role of chemokines in tumor growth. Cancer Lett 256: 137–165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siebenlist U, Franzoso G . (1994). Structure, regulation and function of NF-κB. Annu Rev Cell Biol 10: 405–455.

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Liu Z, Wang L, Zhang X . (2009). NF-κB signaling pathway, inflammation and colorectal cancer. Cell Mol Immunol 6: 327–334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu Y, Zhou BP . (2009). Inflammation: a driving force speeds cancer metastasis. Cell Cycle 8: 3267–3273.

    Article  CAS  PubMed  Google Scholar 

  • Yan J, Aldrich RW . (2010). LRRC26 auxillary protein allows BK channel activation at resting voltage without calcium. Nature 466: 513–516.

    Article  CAS  PubMed  Google Scholar 

  • Yoneda K, Lida H, Endo H, Ozono K, Akiyama T, Takahashi H et al. (2009). Identification of cystatin SN as a novel tumor marker for colorectal cancer. Int J Oncol 35: 33–40.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The CAPC antibody was provided by BD BioSciences Pharmingen as an outcome of Antibody Co-development Collaboration between the NCI and BD BioSciences. We thank William H Wood III (National Institute on Aging) and the Confocal Core Facility members (Center for Cancer Research, NIH) for technical assistance. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and in part by the National Institute on Aging.

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Correspondence to I Pastan.

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Liu, XF., Xiang, L., Zhang, Y. et al. CAPC negatively regulates NF-κB activation and suppresses tumor growth and metastasis. Oncogene 31, 1673–1682 (2012). https://doi.org/10.1038/onc.2011.355

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