Dynamic interactions between cells and extracellular matrix (ECM) through integrins influence most cellular functions. Normal cells, but even more, tumor cells are subjected to different forms of stress, including ischemia, radical oxygen species production, starvation, mechanical stress or genotoxic insults due to anti-cancer drugs or irradiation. In these situations, an adaptative cellular response occurs, integrating a complex network of intracellular signaling modules, which, depending on stress intensity, may result to either damage repair followed by complete restitution of cellular functions, or programmed cell death. Because of its implication in oncogenesis and anti-cancer therapy, cellular stress response has been thoroughly investigated. However, most of these studies have been performed in the context of isolated cells without taking into consideration that most cells are part of the tissue within which they interact with ECM through integrin. Few studies have described the influence of stress on cell-to-ECM interaction. However, one can speculate that, in these conditions, cells could functionally interact with protein microenvironment either to create positive interactions to survive (for example by facilitating protective pathways) or negative interaction to die (for example by facilitating detachment). In this review, we summarize the knowledge relative to the influence of different stress modalities on ECM remodeling, integrin expression and/or function modifications, and possible functional consequences, independently from the cellular model as these findings came from a large variety of cells (mesenchymal, endothelial, muscular, epithelial and glandular) and fields of application (cancer, vascular biology and tissue engineering). Most studies support the general notion that non-lethal stress favors ECM stiffness, integrin activation and enhanced survival. This field opens large perspectives not only in tumor biology but also in anti-cancer therapy by targeting one or several steps of the integrin-mediated signaling pathway, including integrin ligation, or activation of integrin-linked enzymes or integrin adaptors.
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Beinke C, Van Beuningen D, Cordes N . (2003). Ionizing radiation modules of the expression and tyrosine phosphorylation of the focal adhesion-associated proteins focal adhesion kinase (FAK) and its substrates p130cas and paxillin in A549 human lung carcinoma cells in vitro. Int J Radiat Biol 79: 721–731.
Bendall LJ, Makrynikola V, Hutchinson A, Bianchi AC, Bradstock KF, Gottlieb DJ . (1998). Stem cell factor enhances the adhesion of AML cells to fibronectin and augments fibronectin-mediated anti-apoptotic and proliferative signals. Leukemia 12: 1375–1382.
Berrier AL, Yamada KM . (2007). Cell-matrix adhesion. J Cell Physiol 213: 565–573.
Blaschke F, Stawowy P, Goetze S, Hintz O, Grafe M, Kintscher U et al. (2002). Hypoxia activates beta(1)-integrin via ERK 1/2 and p38 MAP kinase in human vascular smooth muscle cells. Biochem Biophys Res Commun 296: 890–896.
Boyer B, Fourtanier A, Kern P, Labat-Robert J . (1992). UVA- and UVB-induced changes in collagen and fibronectin biosynthesis in the skin of hairless mice. J Photochem Photobiol B 14: 247–259.
Buzza MS, Zamurs L, Sun J, Bird CH, Smith AI, Trapani JA et al. (2005). Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin, fibronectin, and laminin. J Biol Chem 280: 23549–23558.
Cabodi S, del Pilar Camacho-Leal M, Di Stefano P, Defilippi P . (2010). Integrin signalling adaptors: not only figurants in the cancer story. Nat Rev Cancer 10: 858–870.
Casanova I, Bosch R, Lasa A, Parreno M, Cespedes MV, Brunet S et al. (2008). A celecoxib derivative inhibits focal adhesion signaling and induces caspase-8-dependent apoptosis in human acute myeloid leukemia cells. Int J Cancer 123: 217–226.
Case D, Irwin D, Ivester C, Harral J, Morris K, Imamura M et al. (2007). Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 292: L154–L164.
Cha MC, Purslow PP . (2010). The activities of MMP-9 and total gelatinase respond differently to substrate coating and cyclic mechanical stretching in fibroblasts and myoblasts. Cell Biol Int 34: 587–591.
Cheng JC, Chou CH, Kuo ML, Hsieh CY . (2006). Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway. Oncogene 25: 7009–7018.
Chiarugi P . (2008). From anchorage dependent proliferation to survival: lessons from redox signalling. IUBMB Life 60: 301–307.
Chiquet M . (1999). Regulation of extracellular matrix gene expression by mechanical stress. Matrix Biol 18: 417–426.
Cordes N, Seidler J, Durzok R, Geinitz H, Brakebusch C . (2006). beta1-integrin-mediated signaling essentially contributes to cell survival after radiation-induced genotoxic injury. Oncogene 25: 1378–1390.
Cowden Dahl KD, Robertson SE, Weaver VM, Simon MC . (2005). Hypoxia-inducible factor regulates alphavbeta3 integrin cell surface expression. Mol Biol Cell 16: 1901–1912.
Cukierman E, Pankov R, Stevens DR, Yamada KM . (2001). Taking cell-matrix adhesions to the third dimension. Science 294: 1708–1712.
Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS . (1999). Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 93: 1658–1667.
De Croos JN, Roughley PJ, Kandel RA . (2010). Improved bioengineered cartilage tissue formation following cyclic compression is dependent on upregulation of MT1-MMP. J Orthop Res 28: 921–927.
De Toni-Costes F, Despeaux M, Bertrand J, Bourogaa E, Ysebaert L, Payrastre B et al. (2010). A New alpha5beta1 integrin-dependent survival pathway through GSK3beta activation in leukemic cells. PLoS One 5: e9807.
De Toni F, Racaud-Sultan C, Chicanne G, Mas VM, Cariven C, Mesange F et al. (2006). A crosstalk between the Wnt and the adhesion-dependent signaling pathways governs the chemosensitivity of acute myeloid leukemia. Oncogene 25: 3113–3122.
Demou ZN . (2010). Gene expression profiles in 3D tumor analogs indicate compressive strain differentially enhances metastatic potential. Ann Biomed Eng 38: 3509–3520.
Desgrosellier JS, Cheresh DA . (2010). Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 10: 9–22.
Di Donato A, Ghiggeri GM, Di Duca M, Jivotenko E, Acinni R, Campolo J et al. (1997). Lysyl oxidase expression and collagen cross-linking during chronic adriamycin nephropathy. Nephron 76: 192–200.
Duensing S, Brevis Nunez F, Meyer N, Anastassiou G, Nasarek A, Grosse J et al. (1996). Exposure to vinblastine modulates beta 1 integrin expression and in vitro binding to extracellular matrix molecules in a human renal carcinoma cell line. Invasion Metastasis 16: 65–72.
Eckes B, Zweers MC, Zhang ZG, Hallinger R, Mauch C, Aumailley M et al. (2006). Mechanical tension and integrin alpha 2 beta 1 regulate fibroblast functions. J Investig Dermatol Symp Proc 11: 66–72.
Estrugo D, Fischer A, Hess F, Scherthan H, Belka C, Cordes N . (2007). Ligand bound beta1 integrins inhibit procaspase-8 for mediating cell adhesion-mediated drug and radiation resistance in human leukemia cells. PLoS One 2: e269.
Fouquet S, Lugo-Martinez VH, Faussat AM, Renaud F, Cardot P, Chambaz J et al. (2004). Early loss of E-cadherin from cell-cell contacts is involved in the onset of Anoikis in enterocytes. J Biol Chem 279: 43061–43069.
Frisch SM, Ruoslahti E . (1997). Integrins and anoikis. Curr Opin Cell Biol 9: 701–706.
Frisch SM, Vuori K, Ruoslahti E, Chan-Hui PY . (1996). Control of adhesion-dependent cell survival by focal adhesion kinase. J Cell Biol 134: 793–799.
Ghosh S, Spagnoli GC, Martin I, Ploegert S, Demougin P, Heberer M et al. (2005). Three-dimensional culture of melanoma cells profoundly affects gene expression profile: a high density oligonucleotide array study. J Cell Physiol 204: 522–531.
Gong LM, Du JB, Shi L, Shi Y, Tang CS . (2004). Effects of endogenous carbon monoxide on collagen synthesis in pulmonary artery in rats under hypoxia. Life Sci 74: 1225–1241.
Guo W, Giancotti FG . (2004). Integrin signalling during tumour progression. Nat Rev Mol Cell Biol 5: 816–826.
Hannafin JA, Attia EA, Henshaw R, Warren RF, Bhargava MM . (2006). Effect of cyclic strain and plating matrix on cell proliferation and integrin expression by ligament fibroblasts. J Orthop Res 24: 149–158.
Hazane F, Valenti K, Sauvaigo S, Peinnequin A, Mouret C, Favier A et al. (2005). Ageing effects on the expression of cell defence genes after UVA irradiation in human male cutaneous fibroblasts using cDNA arrays. J Photochem Photobiol B 79: 171–190.
Hazlehurst LA, Damiano JS, Buyuksal I, Pledger WJ, Dalton WS . (2000). Adhesion to fibronectin via beta1 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR). Oncogene 19: 4319–4327.
Hernandez-Pigeon H, Jean C, Charruyer A, Haure MJ, Baudouin C, Charveron M et al. (2007). UVA induces granzyme B in human keratinocytes through MIF: implication in extracellular matrix remodeling. J Biol Chem 282: 8157–8164.
Hernandez-Pigeon H, Jean C, Charruyer A, Haure MJ, Titeux M, Tonasso L et al. (2006). Human keratinocytes acquire cellular cytotoxicity under UV-B irradiation. Implication of granzyme B and perforin. J Biol Chem 281: 13525–13532.
Hofmann C, Obermeier F, Artinger M, Hausmann M, Falk W, Schoelmerich J et al. (2007). Cell-cell contacts prevent anoikis in primary human colonic epithelial cells. Gastroenterology 132: 587–600.
Horino Y, Takahashi S, Miura T, Takahashi Y . (2002). Prolonged hypoxia accelerates the posttranscriptional process of collagen synthesis in cultured fibroblasts. Life Sci 71: 3031–3045.
Horning JL, Sahoo SK, Vijayaraghavalu S, Dimitrijevic S, Vasir JK, Jain TK et al. (2008). 3-D tumor model for in vitro evaluation of anticancer drugs. Mol Pharm 5: 849–862.
Howe AK, Aplin AE, Juliano RL . (2002). Anchorage-dependent ERK signaling—mechanisms and consequences. Curr Opin Genet Dev 12: 30–35.
Hoyt DG, Rusnak JM, Mannix RJ, Modzelewski RA, Johnson CS, Lazo JS . (1996). Integrin activation suppresses etoposide-induced DNA strand breakage in cultured murine tumor-derived endothelial cells. Cancer Res 56: 4146–4149.
Ingber DE . (2003a). Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116: 1157–1173.
Ingber DE . (2003b). Tensegrity II. How structural networks influence cellular information processing networks. J Cell Sci 116: 1397–1408.
Iovine B, Nino M, Irace C, Bevilacqua MA, Monfrecola G . (2009). Ultraviolet B and A irradiation induces fibromodulin expression in human fibroblasts in vitro. Biochimie 91: 364–372.
Ise K, Sato Y, Matsuyama S, Gunji T, Ishii S, Yamashita M et al. (2004). Transforming growth factor-beta signaling is enhanced following mitomycin-C treatment of islet xenograft. Transplant Proc 36: 1183–1185.
Ishikawa J, Kario K, Matsui Y, Shibasaki S, Morinari M, Kaneda R et al. (2005). Collagen metabolism in extracellular matrix may be involved in arterial stiffness in older hypertensive patients with left ventricular hypertrophy. Hypertens Res 28: 995–1001.
Janig E, Haslbeck M, Aigelsreiter A, Braun N, Unterthor D, Wolf P et al. (2007). Clusterin associates with altered elastic fibers in human photoaged skin and prevents elastin from ultraviolet-induced aggregation in vitro. Am J Pathol 171: 1474–1482.
Jean C, Blanc A, Prade-Houdellier N, Ysebaert L, Hernandez-Pigeon H, Al Saati T et al. (2009). Epidermal growth factor receptor/beta-catenin/T-cell factor 4/matrix metalloproteinase 1: a new pathway for regulating keratinocyte invasiveness after UVA irradiation. Cancer Res 69: 3291–3299.
Jikko A, Hiranuma H, Iwamoto M, Kato Y, Okada Y, Fuchihata H . (1996). Effects of X irradiation on metabolism of proteoglycans. Radiat Res 146: 93–99.
Katsumi A, Naoe T, Matsushita T, Kaibuchi K, Schwartz MA . (2005). Integrin activation and matrix binding mediate cellular responses to mechanical stretch. J Biol Chem 280: 16546–16549.
Keely S, Glover LE, MacManus CF, Campbell EL, Scully MM, Furuta GT et al. (2009). Selective induction of integrin beta1 by hypoxia-inducible factor: implications for wound healing. FASEB J 23: 1338–1346.
Kessler D, Dethlefsen S, Haase I, Plomann M, Hirche F, Krieg T et al. (2001). Fibroblasts in mechanically stressed collagen lattices assume a ‘synthetic’ phenotype. J Biol Chem 276: 36575–36585.
Kim SH, Xia D, Kim SW, Holla V, Menter DG, Dubois RN . (2010). Human enhancer of filamentation 1 Is a mediator of hypoxia-inducible factor-1alpha-mediated migration in colorectal carcinoma cells. Cancer Res 70: 4054–4063.
Kizaki K, Ito R, Okada M, Yoshioka K, Uchide T, Temma K et al. (2006). Enhanced gene expression of myocardial matrix metalloproteinases 2 and 9 after acute treatment with doxorubicin in mice. Pharmacol Res 53: 341–346.
Kligman LH, Gebre M, Alper R, Kefalides NA . (1989). Collagen metabolism in ultraviolet irradiated hairless mouse skin and its correlation to histochemical observations. J Invest Dermatol 93: 210–214.
Kligman LH, Yang S, Schwartz E . (1999). Steady-state mRNA levels of interleukin-1, integrins, cJun, and cFos in hairless mouse skin during short-term chronic UV exposure and the effect of topical tretinoin. Photodermatol Photoimmunol Photomed 15: 198–204.
Kock LM, Schulz RM, van Donkelaar CC, Thummler CB, Bader A, Ito K . (2009). RGD-dependent integrins are mechanotransducers in dynamically compressed tissue-engineered cartilage constructs. J Biomech 42: 2177–2182.
Koike T, Kimura N, Miyazaki K, Yabuta T, Kumamoto K, Takenoshita S et al. (2004). Hypoxia induces adhesion molecules on cancer cells: a missing link between Warburg effect and induction of selectin-ligand carbohydrates. Proc Natl Acad Sci USA 101: 8132–8137.
Kong T, Eltzschig HK, Karhausen J, Colgan SP, Shelley CS . (2004). Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction of beta2 integrin gene expression. Proc Natl Acad Sci USA 101: 10440–10445.
Kozlova NI, Morozevich GE, Shtil AA, Berman AE . (2004). Multidrug-resistant tumor cells with decreased malignancy: a role for integrin alphavbeta3. Biochem Biophys Res Commun 316: 1173–1177.
Kubota Y, Kleinman HK, Martin GR, Lawley TJ . (1988). Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures. J Cell Biol 107: 1589–1598.
Lahiji K, Polotsky A, Hungerford DS, Frondoza CG . (2004). Cyclic strain stimulates proliferative capacity, alpha2 and alpha5 integrin, gene marker expression by human articular chondrocytes propagated on flexible silicone membranes. In vitro Cell Dev Biol Anim 40: 138–142.
Lambert CA, Soudant EP, Nusgens BV, Lapiere CM . (1992). Pretranslational regulation of extracellular matrix macromolecules and collagenase expression in fibroblasts by mechanical forces. Lab Invest 66: 444–451.
Landowski TH, Olashaw NE, Agrawal D, Dalton WS . (2003). Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-kappa B (RelB/p50) in myeloma cells. Oncogene 22: 2417–2421.
Lee SH, Koo KH, Park JW, Kim HJ, Ye SK, Park JB et al. (2009). HIF-1 is induced via EGFR activation and mediates resistance to anoikis-like cell death under lipid rafts/caveolae-disrupting stress. Carcinogenesis 30: 1997–2004.
Lee SH, Lee YJ, Han HJ . (2011). Role of hypoxia-induced fibronectin-integrin beta1 expression in embryonic stem cell proliferation and migration: Involvement of PI3K/Akt and FAK. J Cell Physiol 226: 484–493.
Liang Y, Meleady P, Cleary I, McDonnell S, Connolly L, Clynes M . (2001). Selection with melphalan or paclitaxel (Taxol) yields variants with different patterns of multidrug resistance, integrin expression and in vitro invasiveness. Eur J Cancer 37: 1041–1052.
Lugo-Martinez VH, Petit CS, Fouquet S, Le Beyec J, Chambaz J, Pincon-Raymond M et al. (2009). Epidermal growth factor receptor is involved in enterocyte anoikis through the dismantling of E-cadherin-mediated junctions. Am J Physiol Gastrointest Liver Physiol 296: G235–G244.
Matsunaga T, Fukai F, Miura S, Nakane Y, Owaki T, Kodama H et al. (2008). Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin effectively overcomes cell adhesion-mediated drug resistance of acute myelogenous leukemia. Leukemia 22: 353–360.
Matsunaga T, Takemoto N, Sato T, Takimoto R, Tanaka I, Fujimi A et al. (2003). Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat Med 9: 1158–1165.
Meads MB, Hazlehurst LA, Dalton WS . (2008). The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin Cancer Res 14: 2519–2526.
Milner R, Hung S, Erokwu B, Dore-Duffy P, LaManna JC, del Zoppo GJ . (2008). Increased expression of fibronectin and the alpha 5 beta 1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia. Mol Cell Neurosci 38: 43–52.
Minchinton AI, Tannock IF . (2006). Drug penetration in solid tumours. Nat Rev Cancer 6: 583–592.
Miyazaki Y, Hara A, Kato K, Oyama T, Yamada Y, Mori H et al. (2008). The effect of hypoxic microenvironment on matrix metalloproteinase expression in xenografts of human oral squamous cell carcinoma. Int J Oncol 32: 145–151.
Miyoshi A, Kitajima Y, Ide T, Ohtaka K, Nagasawa H, Uto Y et al. (2006). Hypoxia accelerates cancer invasion of hepatoma cells by upregulating MMP expression in an HIF-1alpha-independent manner. Int J Oncol 29: 1533–1539.
Monferran S, Skuli N, Delmas C, Favre G, Bonnet J, Cohen-Jonathan-Moyal E et al. (2008). Alphavbeta3 and alphavbeta5 integrins control glioma cell response to ionising radiation through ILK and RhoB. Int J Cancer 123: 357–364.
Moore SW, Roca-Cusachs P, Sheetz MP . (2010). Stretchy proteins on stretchy substrates: the important elements of integrin-mediated rigidity sensing. Dev Cell 19: 194–206.
Munoz-Najar UM, Neurath KM, Vumbaca F, Claffey KP . (2006). Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation. Oncogene 25: 2379–2392.
Munoz J, Zhou Y, Jarrett HW . (2010). LG4-5 domains of laminin-211 binds alpha-dystroglycan to allow myotube attachment and prevent anoikis. J Cell Physiol 222: 111–119.
Muszynska A, Wolczynski S, Palka J . (2001). The mechanism for anthracycline-induced inhibition of collagen biosynthesis. Eur J Pharmacol 411: 17–25.
Myllyharju J, Schipani E . (2010). Extracellular matrix genes as hypoxia-inducible targets. Cell Tissue Res 339: 19–29.
Neitmann M, Alexander M, Brinckmann J, Schlenke P, Tronnier M . (1999). Attachment and chemotaxis of melanocytes after ultraviolet irradiation in vitro. Br J Dermatol 141: 794–801.
Netti PA, Berk DA, Swartz MA, Grodzinsky AJ, Jain RK . (2000). Role of extracellular matrix assembly in interstitial transport in solid tumors. Cancer Res 60: 2497–2503.
Noborio-Hatano K, Kikuchi J, Takatoku M, Shimizu R, Wada T, Ueda M et al. (2009). Bortezomib overcomes cell-adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma. Oncogene 28: 231–242.
Orr AW, Ginsberg MH, Shattil SJ, Deckmyn H, Schwartz MA . (2006). Matrix-specific suppression of integrin activation in shear stress signaling. Mol Biol Cell 17: 4686–4697.
Oswald J, Steudel C, Salchert K, Joergensen B, Thiede C, Ehninger G et al. (2006). Gene-expression profiling of CD34+ hematopoietic cells expanded in a collagen I matrix. Stem Cells 24: 494–500.
Provenzano PP, Inman DR, Eliceiri KW, Keely PJ . (2009). Matrix density-induced mechanoregulation of breast cell phenotype, signaling and gene expression through a FAK-ERK linkage. Oncogene 28: 4326–4343.
Quan T, He T, Kang S, Voorhees JJ, Fisher GJ . (2004). Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-beta type II receptor/Smad signaling. Am J Pathol 165: 741–751.
Repesh LA, Drake SR, Warner MC, Downing SW, Jyring R, Seftor EA et al. (1993). Adriamycin-induced inhibition of melanoma cell invasion is correlated with decreases in tumor cell motility and increases in focal contact formation. Clin Exp Metastasis 11: 91–102.
Rohwer N, Welzel M, Daskalow K, Pfander D, Wiedenmann B, Detjen K et al. (2008). Hypoxia-inducible factor 1alpha mediates anoikis resistance via suppression of alpha5 integrin. Cancer Res 68: 10113–10120.
Salo S, Boutaud A, Hansen AJ, He L, Sun Y, Morales S et al. (2009). Antibodies blocking adhesion and matrix binding domains of laminin-332 inhibit tumor growth and metastasis in vivo. Int J Cancer 125: 1814–1825.
Sasaki T, Holeyfield KC, Uitto J . (1987). Doxorubicin-induced inhibition of prolyl hydroxylation during collagen biosynthesis in human skin fibroblast cultures. Relevance to imparied wound healing. J Clin Invest 80: 1735–1741.
Sastry SK, Lakonishok M, Thomas DA, Muschler J, Horwitz AF . (1996). Integrin alpha subunit ratios, cytoplasmic domains, and growth factor synergy regulate muscle proliferation and differentiation. J Cell Biol 133: 169–184.
Sawada Y, Sheetz MP . (2002). Force transduction by Triton cytoskeletons. J Cell Biol 156: 609–615.
Schmidmaier R, Baumann P, Simsek M, Dayyani F, Emmerich B, Meinhardt G . (2004). The HMG-CoA reductase inhibitor simvastatin overcomes cell adhesion-mediated drug resistance in multiple myeloma by geranylgeranylation of Rho protein and activation of Rho kinase. Blood 104: 1825–1832.
Schuetz JD, Schuetz EG . (1993). Extracellular matrix regulation of multidrug resistance in primary monolayer cultures of adult rat hepatocytes. Cell Growth Differ 4: 31–40.
Schwartz MA, DeSimone DW . (2008). Cell adhesion receptors in mechanotransduction. Curr Opin Cell Biol 20: 551–556.
Sethi T, Rintoul RC, Moore SM, MacKinnon AC, Salter D, Choo C et al. (1999). Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat Med 5: 662–668.
Shyy JY, Chien S . (1997). Role of integrins in cellular responses to mechanical stress and adhesion. Curr Opin Cell Biol 9: 707–713.
Skuli N, Monferran S, Delmas C, Favre G, Bonnet J, Toulas C et al. (2009). Alphavbeta3/alphavbeta5 integrins-FAK-RhoB: a novel pathway for hypoxia regulation in glioblastoma. Cancer Res 69: 3308–3316.
Song JH, Kim SH, Cho D, Lee IK, Kim HJ, Kim TS . (2009). Enhanced invasiveness of drug-resistant acute myeloid leukemia cells through increased expression of matrix metalloproteinase-2. Int J Cancer 125: 1074–1081.
Sood AK, Armaiz-Pena GN, Halder J, Nick AM, Stone RL, Hu W et al. (2010). Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis. J Clin Invest 120: 1515–1523.
St Croix B, Florenes VA, Rak JW, Flanagan M, Bhattacharya N, Slingerland JM et al. (1996). Impact of the cyclin-dependent kinase inhibitor p27Kip1 on resistance of tumor cells to anticancer agents. Nat Med 2: 1204–1210.
Sullivan R, Graham CH . (2007). Hypoxia-driven selection of the metastatic phenotype. Cancer Metastasis Rev 26: 319–331.
Ta HQ, Thomas KS, Schrecengost RS, Bouton AH . (2008). A novel association between p130Cas and resistance to the chemotherapeutic drug adriamycin in human breast cancer cells. Cancer Res 68: 8796–8804.
Takahashi I, Onodera K, Sasano Y, Mizoguchi I, Bae JW, Mitani H et al. (2003). Effect of stretching on gene expression of beta1 integrin and focal adhesion kinase and on chondrogenesis through cell-extracellular matrix interactions. Eur J Cell Biol 82: 182–192.
Tanjoni I, Walsh C, Uryu S, Tomar A, Nam JO, Mielgo A et al. (2010). PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments. Cancer Biol Ther 9: 764–777.
Thaker PH, Han LY, Kamat AA, Arevalo JM, Takahashi R, Lu C et al. (2006). Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med 12: 939–944.
Thao le B, Vu HA, Yasuda K, Taniguchi S, Yagasaki F, Taguchi T et al. (2009). Cas-L was overexpressed in imatinib-resistant gastrointestinal stromal tumor cells. Cancer Biol Ther 8: 683–688.
Ulrich TA, de Juan Pardo EM, Kumar S . (2009). The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells. Cancer Res 69: 4167–4174.
van Nimwegen MJ, Huigsloot M, Camier A, Tijdens IB, van de Water B . (2006). Focal adhesion kinase and protein kinase B cooperate to suppress doxorubicin-induced apoptosis of breast tumor cells. Mol Pharmacol 70: 1330–1339.
Varner JA, Emerson DA, Juliano RL . (1995). Integrin alpha 5 beta 1 expression negatively regulates cell growth: reversal by attachment to fibronectin. Mol Biol Cell 6: 725–740.
Verhaar R, Dekkers DW, De Cuyper IM, Ginsberg MH, de Korte D, Verhoeven AJ . (2008). UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin alphaIIbbeta3. Blood 112: 4935–4939.
Walsh C, Tanjoni I, Uryu S, Tomar A, Nam JO, Luo H et al. (2010). Oral delivery of PND-1186 FAK inhibitor decreases tumor growth and spontaneous breast to lung metastasis in pre-clinical models. Cancer Biol Ther 9: 778–790.
Walton HL, Corjay MH, Mohamed SN, Mousa SA, Santomenna LD, Reilly TM . (2000). Hypoxia induces differential expression of the integrin receptors alpha(vbeta3) and alpha(vbeta5) in cultured human endothelial cells. J Cell Biochem 78: 674–680.
Wary KK, Mainiero F, Isakoff SJ, Marcantonio EE, Giancotti FG . (1996). The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Cell 87: 733–743.
Weber LM, Hayda KN, Anseth KS . (2008). Cell-matrix interactions improve beta-cell survival and insulin secretion in three-dimensional culture. Tissue Eng Part A 14: 1959–1968.
Wen H, Blume PA, Sumpio BE . (2009). Role of integrins and focal adhesion kinase in the orientation of dermal fibroblasts exposed to cyclic strain. Int Wound J 6: 149–158.
Westhoff MA, Zhou S, Bachem MG, Debatin KM, Fulda S . (2008). Identification of a novel switch in the dominant forms of cell adhesion-mediated drug resistance in glioblastoma cells. Oncogene 27: 5169–5181.
Wykoff CC, Sotiriou C, Cockman ME, Ratcliffe PJ, Maxwell P, Liu E et al. (2004). Gene array of VHL mutation and hypoxia shows novel hypoxia-induced genes and that cyclin D1 is a VHL target gene. Br J Cancer 90: 1235–1243.
Yao J, Liu Y, Wang X, Shen Y, Yuan S, Wan Y et al. (2009). UVB radiation induces human lens epithelial cell migration via NADPH oxidase-mediated generation of reactive oxygen species and up-regulation of matrix metalloproteinases. Int J Mol Med 24: 153–159.
Zamir E, Geiger B . (2001). Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci 114: 3583–3590.
We would like to acknowledge Dr Claire RACAUD-SULTAN for the advised comments.
The authors declare no conflict of interest.
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Jean, C., Gravelle, P., Fournie, JJ. et al. Influence of stress on extracellular matrix and integrin biology. Oncogene 30, 2697–2706 (2011). https://doi.org/10.1038/onc.2011.27
- integrin biology
- cellular response
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