Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer

Yu Chang Chuang1, Chang-Jer Wu2, Yuling Lin1, Shey-Cherng Tzou2, Ching-Te Chuang2, Ting Yan Jian2, Pin Rong Chen2, Yuan Chang3, Chi Hsin Lin4, Tse-Hung Huang5, Chao Ching Wang5, Yi Lin Chan6, Kuang‐Wen Liao2
1Departmet of Biological Science and Technology, National Chiao Tung University, 75 Bo-Ai Street, Hsinchu, 300, Taiwan, Republic of China
2Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, 75 Bo-Ai Street, Hsinchu, 300, Taiwan, Republic of China
3Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan Republic of China
4Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China
5Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China
6Department of Life Science, Chinese Culture University, 55, Hwa-Kang Rd., Yang-Ming-Shan, Taipei, 11114, Taiwan, Republic of China

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Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin D, Forman D, Bray F. GLOBOCAN 2012 v1. 0, cancer incidence and mortality worldwide: IARC CancerBase no. 11 [internet]. 2013. International Agency for Research on Cancer.globocan iarc fr/Default aspx: Lyon, France; 2014.

Bria E, De Manzoni G, Beghelli S, Tomezzoli A, Barbi S, Di Gregorio C, Scardoni M, Amato E, Frizziero M, Sperduti I, et al. A clinical-biological risk stratification model for resected gastric cancer: prognostic impact of Her2, Fhit, and APC expression status. Ann Oncol. 2013;24:693–701.

Yamamoto H, Watanabe Y, Maehata T, Morita R, Yoshida Y, Oikawa R, Ishigooka S, Ozawa S, Matsuo Y, Hosoya K, et al. An updated review of gastric cancer in the next-generation sequencing era: insights from bench to bedside and vice versa. World J Gastroenterol. 2014;20:3927–37.

Akhondi-Meybodi M, Ghane M, Akhondi-Meybodi S, Dashti G. Five-year survival rate for gastric cancer in Yazd Province, Central Iran, from 2001 to 2008. Middle East J Dig Dis. 2017;9:39–48.

Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, et al. Treatment of gastric cancer. World J Gastroenterol. 2014;20:1635–49.

Digklia A, Wagner AD. Advanced gastric cancer: current treatment landscape and future perspectives. World J Gastroenterol. 2016;22:2403–14.

Smyth EC, Cunningham D. Targeted therapy for gastric cancer. Curr Treat Options in Oncol. 2012;13:377–89.

Kanat O, O'Neil B, Shahda S. Targeted therapy for advanced gastric cancer: a review of current status and future prospects. World J Gastrointest Oncol. 2015;7:401–10.

Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523–9.

Phan DAT, Nguyen VT, Hua TNH, Ngo QD, Doan TPT, Nguyen ST, Thai AT, Nguyen VT. HER2 status and its heterogeneity in gastric carcinoma of Vietnamese patient. J Pathol Transl Med. 2017;51:396–402.

Ohtsu A, Shah MA, Cutsem EV, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–76.

Shen L, Li J, Xu J, Pan H, Dai G, Qin S, Wang L, Wang J, Yang Z, Shu Y, et al. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015;18:168–76.

Tabernero J, Hoff PM, Shen L, Ohtsu A, Yu R, Eng-Wong J, Kang Y-K. Pertuzumab (P) with trastuzumab (T) and chemotherapy (CTX) in patients (pts) with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer: an international phase III study (JACOB). J Clin Oncol. 2013;31:TPS4150–0.

Plow EF, Haas TA, Zhang L, Loftus J, Smith JW. Ligand binding to integrins. J Biol Chem. 2000;275:21785–8.

Tuckwell D, Calderwood DA, Green LJ, Humphries MJ. Integrin alpha 2 I-domain is a binding site for collagens. J Cell Sci. 1995;108(Pt 4):1629–37.

Whittard JD, Craig SE, Mould AP, Koch A, Pertz O, Engel J, Humphries MJ. E-cadherin is a ligand for integrin α2β1. Matrix Biol. 2002;21:525–32.

Giancotti FG, Ruoslahti E. Integrin signaling. Science. 1999;285:1028–32.

Stipp CS. Laminin-binding integrins and their tetraspanin partners as potential antimetastatic targets. Expert Rev Mol Med. 2010;12:e3.

Gout SP, Jacquier-Sarlin MR, Rouard-Talbot L, Rousselle P, Block MR. RhoA-dependent switch between alpha2beta1 and alpha3beta1 integrins is induced by laminin-5 during early stage of HT-29 cell differentiation. Mol Biol Cell. 2001;12:3268–81.

Madamanchi A, Santoro SA, Zutter MM. alpha2beta1 Integrin. Adv Exp Med Biol. 2014;819:41–60.

Silva R, D'Amico G, Hodivala-Dilke KM, Reynolds LE. Integrins: the keys to unlocking angiogenesis. Arterioscler Thromb Vasc Biol. 2008;28:1703–13.

Zutter MM, Santoro SA. Widespread histologic distribution of the alpha 2 beta 1 integrin cell-surface collagen receptor. Am J Pathol. 1990;137:113–20.

McCall-Culbreath KD, Zutter MM. Collagen receptor integrins: rising to the challenge. Curr Drug Targets. 2008;9:139–49.

Yang C, Zeisberg M, Lively JC, Nyberg P, Afdhal N, Kalluri R. Integrin alpha1beta1 and alpha2beta1 are the key regulators of hepatocarcinoma cell invasion across the fibrotic matrix microenvironment. Cancer Res. 2003;63:8312–7.

San Antonio JD, Zoeller JJ, Habursky K, Turner K, Pimtong W, Burrows M, Choi S, Basra S, Bennett JS, DeGrado WF, Iozzo RV. A key role for the integrin alpha2beta1 in experimental and developmental angiogenesis. Am J Pathol. 2009;175:1338–47.

Hall CL, Dubyk CW, Riesenberger TA, Shein D, Keller ET, van Golen KL. Type I collagen receptor (alpha2beta1) signaling promotes prostate cancer invasion through RhoC GTPase. Neoplasia. 2008;10:797–803.

Mizejewski GJ. Role of integrins in cancer: survey of expression patterns. Proc Soc Exp Biol Med. 1999;222:124–38.

Danen EH. Integrins: regulators of tissue function and cancer progression. Curr Pharm Des. 2005;11:881–91.

Danen EH, Sonnenberg A. Integrins in regulation of tissue development and function. J Pathol. 2003;201:632–41.

Guo W, Giancotti FG. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol. 2004;5:816–26.

Calleros L, Lasa M, Rodriguez-Alvarez FJ, Toro MJ, Chiloeches A. RhoA and p38 MAPK mediate apoptosis induced by cellular cholesterol depletion. Apoptosis. 2006;11:1161–73.

Kamel WA, Sugihara E, Nobusue H, Yamaguchi-Iwai S, Onishi N, Maki K, Fukuchi Y, Matsuo K, Muto A, Saya H, Shimizu T. Simvastatin-induced apoptosis in osteosarcoma cells: a key role of RhoA-AMPK/p38 MAPK signaling in antitumor activity. Mol Cancer Ther. 2017;16:182–92.

Leslie H, Sobin MKG. Christian Wittekind: TNM classification of malignant Tumours. 7th ed. Oxford: Wiley-Blackwell; 2011.

Pal N, Axisa B, Yusof S, Newcombe RG, Wemyss-Holden S, Rhodes M, Lewis MP. Volume and outcome for major upper GI surgery in England. J Gastrointest Surg. 2008;12:353–7.

Kang B, Guo RF, Tan XH, Zhao M, Tang ZB, Lu YY. Expression status of ataxia-telangiectasia-mutated gene correlated with prognosis in advanced gastric cancer. Mutat Res. 2008;638:17–25.

Weledji EP. How surgery can improve multimodal treatment of gastric cancer?Annals of Laparoscopic and Endoscopic. Surgery. 2016;1

Kurokawa T, Masuda T. A statistics about the causes of delay in the diagnosis of stomach cancer. Tohoku J Exp Med. 1951;54:294.

Kanagavel D, Fedyanin M, Tryakin A, Tjulandin S. Second-line treatment of metastatic gastric cancer: current options and future directions. World J Gastroenterol. 2015;21:11621–35.

Tran PN, Sarkissian S, Chao J, Klempner SJ. PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence. Gastrointestinal cancer : targets and therapy. 2017;7:1–11.

Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, et al. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1467–82.

Lee SY, Oh SC. Changing strategies for target therapy in gastric cancer. World J Gastroenterol. 2016;22:1179–89.

Marin JJ, Al-Abdulla R, Lozano E, Briz O, Bujanda L, Banales JM, Macias RI. Mechanisms of resistance to chemotherapy in gastric cancer. Anti Cancer Agents Med Chem. 2016;16:318–34.

Shi WJ, Gao JB. Molecular mechanisms of chemoresistance in gastric cancer. World J Gastrointest Oncol. 2016;8:673–81.

Shimoyama S. Unraveling trastuzumab and lapatinib inefficiency in gastric cancer: future steps (review). Mol Clin Oncol. 2014;2:175–81.

Chen J, Liu NN, Li JQ, Yang L, Zeng Y, Zhao XM, Xu LL, Luo X, Wang B, Wang XR. Association between ITGA2 C807T polymorphism and gastric cancer risk. World J Gastroenterol. 2011;17:2860–6.

Langsenlehner U, Renner W, Yazdani-Biuki B, Eder T, Wascher TC, Paulweber B, Clar H, Hofmann G, Samonigg H, Krippl P. Integrin alpha-2 and beta-3 gene polymorphisms and breast cancer risk. Breast Cancer Res Treat. 2006;97:67–72.

Chin SP, Marthick JR, West AC, Short AK, Chuckowree J, Polanowski AM, Thomson RJ, Holloway AF, Dickinson JL. Regulation of the ITGA2 gene by epigenetic mechanisms in prostate cancer. Prostate. 2015;75:723–34.

Chan BM, Matsuura N, Takada Y, Zetter BR, Hemler ME. In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Science. 1991;251:1600–2.

Ura H, Denno R, Hirata K, Yamaguchi K, Yasoshima T. Separate functions of alpha2beta1 and alpha3beta1 integrins in the metastatic process of human gastric carcinoma. Surg Today. 1998;28:1001–6.

Wu YJ, Pagel MA, Muldoon LL, Fu R, Neuwelt EA. High alphav integrin level of cancer cells is associated with development of brain metastasis in Athymic rats. Anticancer Res. 2017;37:4029–40.

Cai QQ, Dong YW, Wang R, Qi B, Guo JX, Pan J, Liu YY, Zhang CY, Wu XZ. MiR-124 inhibits the migration and invasion of human hepatocellular carcinoma cells by suppressing integrin alphaV expression. Sci Rep. 2017;7:40733.

Neisch AL, Speck O, Stronach B, Fehon RG. Rho1 regulates apoptosis via activation of the JNK signaling pathway at the plasma membrane. J Cell Biol. 2010;189:311–23.

Tsai NP, Wei LN. RhoA/ROCK1 signaling regulates stress granule formation and apoptosis. Cell Signal. 2010;22:668–75.

Stankiewicz TR, Linseman DA. Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration. Front Cell Neurosci. 2014;8

Rodriguez J, Lazebnik Y. Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev. 1999;13:3179–84.

Gogvadze V, Orrenius S, Zhivotovsky B. Multiple pathways of cytochrome c release from mitochondria in apoptosis. Biochim Biophys Acta. 2006;1757:639–47.

Nhan TQ, Liles WC, Schwartz SM. Physiological functions of caspases beyond cell death. Am J Pathol. 2006;169:729–37.

Bratton SB, Salvesen GS. Regulation of the Apaf-1-caspase-9 apoptosome. J Cell Sci. 2010;123:3209–14.

Zhang M, Zheng J, Nussinov R, Ma B. Release of cytochrome C from Bax pores at the mitochondrial membrane. Sci Rep. 2017;7:2635.

De Chiara G, Marcocci ME, Torcia M, Lucibello M, Rosini P, Bonini P, Higashimoto Y, Damonte G, Armirotti A, Amodei S, et al. Bcl-2 phosphorylation by p38 MAPK: identification of target sites and biologic consequences. J Biol Chem. 2006;281:21353–61.

He W, Zhang MF, Ye J, Jiang TT, Fang X, Song Y. Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules. J Zhejiang Univ Sci B. 2010;11:654–60.

Bachelor MA, Bowden GT. Ultraviolet A-induced modulation of Bcl-XL by p38 MAPK in human keratinocytes: post-transcriptional regulation through the 3′-untranslated region. J Biol Chem. 2004;279:42658–68.

Cai B, Xia Z. p38 MAP kinase mediates arsenite-induced apoptosis through FOXO3a activation and induction of Bim transcription. Apoptosis. 2008;13:803–10.

Porras A, Zuluaga S, Black E, Valladares A, Alvarez AM, Ambrosino C, Benito M, Nebreda AR. p38α Mitogen-activated Protein Kinase Sensitizes Cells to Apoptosis Induced by Different Stimuli. Mol Biol Cell. 2004;15:922–33.

Kirfel G, Rigort A, Borm B, Herzog V. Cell migration: mechanisms of rear detachment and the formation of migration tracks. Eur J Cell Biol. 2004;83:717–24.

Bugyi B, Carlier M-F. Control of actin filament Treadmilling in cell motility. Annu Rev Biophys. 2010;39:449–70.

Knecht DA, LaFleur RA, Kahsai AW, Argueta CE, Beshir AB, Fenteany G. Cucurbitacin I inhibits cell motility by indirectly interfering with actin dynamics. PLoS One. 2010;5:e14039.

Le Clainche C, Carlier M-F. Regulation of actin assembly associated with protrusion and adhesion in cell migration. Physiol Rev. 2008;88:489–513.

Huang L, Wu RL, Xu AM. Epithelial-mesenchymal transition in gastric cancer. Am J Transl Res. 2015;7:2141–58.

Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15:178–96.

Peng Z, Wang CX, Fang EH, Wang GB, Tong Q. Role of epithelial-mesenchymal transition in gastric cancer initiation and progression. World J Gastroenterol. 2014;20:5403–10.

Wolfenson H, Lavelin I, Geiger B. Dynamic regulation of the structure and functions of integrin adhesions. Dev Cell. 2013;24:447–58.

Khyrul WA, LaLonde DP, Brown MC, Levinson H, Turner CE. The integrin-linked kinase regulates cell morphology and motility in a rho-associated kinase-dependent manner. J Biol Chem. 2004;279:54131–9.

Delon I, Brown NH. Integrins and the actin cytoskeleton. Curr Opin Cell Biol. 2007;19:43–50.

Price LS, Leng J, Schwartz MA, Bokoch GM. Activation of Rac and Cdc42 by integrins mediates cell spreading. Mol Biol Cell. 1998;9:1863–71.

Keely PJ, Westwick JK, Whitehead IP, Der CJ, Parise LV. Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K. Nature. 1997;390:632–6.

Deroanne C, Vouret-Craviari V, Wang B, Pouyssegur J. EphrinA1 inactivates integrin-mediated vascular smooth muscle cell spreading via the Rac/PAK pathway. J Cell Sci. 2003;116:1367–76.

Arthur WT, Noren NK, Burridge K. Regulation of rho family GTPases by cell-cell and cell-matrix adhesion. Biol Res. 2002;35:239–46.

Rohatgi R, Ho HY, Kirschner MW. Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4, 5-bisphosphate. J Cell Biol. 2000;150:1299–310.

Martinez-Quiles N, Rohatgi R, Anton IM, Medina M, Saville SP, Miki H, Yamaguchi H, Takenawa T, Hartwig JH, Geha RS, Ramesh N. WIP regulates N-WASP-mediated actin polymerization and filopodium formation. Nat Cell Biol. 2001;3:484–91.

Kato T, Kawai K, Egami Y, Kakehi Y, Araki N. Rac1-dependent lamellipodial motility in prostate cancer PC-3 cells revealed by optogenetic control of Rac1 activity. PLoS One. 2014;9:e97749.

Steffen A, Rottner K, Ehinger J, Innocenti M, Scita G, Wehland J, Stradal TE. Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. EMBO J. 2004;23:749–59.

Canel M, Serrels A, Frame MC, Brunton VG. E-cadherin-integrin crosstalk in cancer invasion and metastasis. J Cell Sci. 2013;126:393–401.

Patel S, Takagi KI, Suzuki J, Imaizumi A, Kimura T, Mason RM, Kamimura T, Zhang Z. RhoGTPase activation is a key step in renal epithelial mesenchymal transdifferentiation. J Am Soc Nephrol. 2005;16:1977–84.

Chen IJ, Chuang CH, Hsieh YC, Lu YC, Lin WW, Huang CC, Cheng TC, Cheng YA, Cheng KW, Wang YT, et al. Selective antibody activation through protease-activated pro-antibodies that mask binding sites with inhibitory domains. Sci Rep. 2017;7:11587.

Erster O, Thomas JM, Hamzah J, Jabaiah AM, Getz JA, Schoep TD, Hall SS, Ruoslahti E, Daugherty PS. Site-specific targeting of antibody activity in vivo mediated by disease-associated proteases. J Control Release. 2012;161:804–12.

Chames P, Van Regenmortel M, Weiss E, Baty D. Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol. 2009;157:220–33.