Skip to main content Accessibility help
×
Home
Hostname: page-component-59b7f5684b-2bkkj Total loading time: 0.437 Render date: 2022-09-26T14:15:33.266Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "displayNetworkTab": true, "displayNetworkMapGraph": false, "useSa": true } hasContentIssue true

ITGB1 Enhances the Proliferation, Survival, and Motility in Gastric Cancer Cells

Published online by Cambridge University Press:  29 July 2021

Sinan Cheng
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
Xinyao Li
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
Yue Yuan
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
Chenshuang Jia
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
Lirong Chen
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
Qian Gao
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
Zheng Lu
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
Ruina Yang
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
Guochao Nie
Affiliation:
Guangxi Key Laboratory of Agricultural Resource Chemistry and Biotechnology, Yulin Normal University, Yulin, Guangxi537000, China
Jin Yang
Affiliation:
College of Life Sciences, Northwest University, Xi'an, Shaanxi710069, China
Wei Duan
Affiliation:
School of Medicine, Deakin University, Waurn Ponds, VIC3216, Australia
Li Xiao*
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
Yingchun Hou*
Affiliation:
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi710119, China
*
*Corresponding authors: Yingchun Hou, E-mail: ychhou@snnu.edu.cn; Li Xiao, E-mail: xiaoli@snnu.edu.cn.
*Corresponding authors: Yingchun Hou, E-mail: ychhou@snnu.edu.cn; Li Xiao, E-mail: xiaoli@snnu.edu.cn.

Abstract

ITGB1 (Integrin β1, CD29) is a member of the integrin family and has a role as a major adhesion receptor. Gastric cancer (GC) is an important cause of mortality worldwide, especially in China. As a potential cancer enhancer, the role ITGB1 plays in GC progression remains unclear. In the current study, our assay on the databases of tumoassociated gene expression and interaction found that the high expression of ITGB1 was closely correlated with the poor prognosis of GC patients. To explore the roles, ITGB1 plays in GC progression, and an ITGB1-deleted cell line (ITGB1−/−SGC7901) was generated using the CRISPR/Cas9 method. The tumor malignancy-associated cell behaviors and microstructures were detected, imaged, and analyzed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), wound healing, transwell, scanning electron microscopy, laser scanning confocal microscopy, and others. The results indicated that ITGB1 deletion decreased the GC cell proliferation and motility, and inhibited motility-relevant microstructures, such as pseudopodia and filopodia, markedly in ITGB1-deleted SGC7901 cells. The analysis of STRING database and western blots indicated that ITGB1 contributes to the malignancy of GC mediated by Src-mediated FAK/PI3K/Akt signaling pathways. Taken together, the results showed that ITGB1 may be a potential targeting marker for GC diagnosis and therapy in the future.

Type
Biological Applications
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press on behalf of the Microscopy Society of America

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alanko, J & Ivaska, J (2016). Endosomes: Emerging platforms for integrin-mediated FAK signalling. Trends Cell Biol 26(6), 391398.10.1016/j.tcb.2016.02.001CrossRefGoogle ScholarPubMed
Askari, JA, Buckley, PA, Mould, AP & Humphries, MJ (2009). Linking integrin conformation to function. J Cell Sci 122(Pt 2), 165170.10.1242/jcs.018556CrossRefGoogle Scholar
Attieh, Y, Clark, AG, Grass, C, Richon, S, Pocard, M, Mariani, P, Elkhatib, N, Betz, T, Gurchenkov, B & Vignjevic, DM (2017). Cancer-associated fibroblasts lead tumor invasion through integrin-β3-dependent fibronectin assembly. J Cell Biol 216(11), 35093520.CrossRefGoogle ScholarPubMed
Bray, F, Ferlay, J, Soerjomataram, I, Siegel, RL, Torre, LA & Jemal, A (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6), 394424.10.3322/caac.21492CrossRefGoogle ScholarPubMed
Brooks, PC, Strömblad, S, Sanders, LC, von Schalscha, TL, Aimes, RT, Stetler-Stevenson, WG, Quigley, JP & Cheresh, DA (1996). Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin αvβ3. Cell 85(5), 683693.10.1016/S0092-8674(00)81235-0CrossRefGoogle Scholar
Campbell, ID & Humphries, MJ (2011). Integrin structure, activation, and interactions. Cold Spring Harbor Perspect Biol 3(3), a004994.10.1101/cshperspect.a004994CrossRefGoogle ScholarPubMed
Carbonell, WS, DeLay, M, Jahangiri, A, Park, CC & Aghi, MK (2013). beta1 integrin targeting potentiates antiangiogenic therapy and inhibits the growth of bevacizumab-resistant glioblastoma. Cancer Res 73(10), 31453154.10.1158/0008-5472.CAN-13-0011CrossRefGoogle ScholarPubMed
Chang, C, Goel, HL, Gao, H, Pursell, B, Shultz, LD, Greiner, DL, Ingerpuu, S, Patarroyo, M, Cao, S, Lim, E, Mao, J, McKee, KK, Yurchenco, PD & Mercurio, AM (2015). A laminin 511 matrix is regulated by TAZ and functions as the ligand for the alpha6Bbeta1 integrin to sustain breast cancer stem cells. Genes Dev 29, 16.10.1101/gad.253682.114CrossRefGoogle ScholarPubMed
Chuang, YC, Wu, HY, Lin, YL, Tzou, SC, Chuang, CH, Jian, TY, Chen, PR, Chang, YC, Lin, CH, Huang, TH, Wang, CC, Chan, YL & Liao, KW (2018). Blockade of ITGA2 induces apoptosis and inhibits cell migration in gastric cancer. Biol Proced Online 20, 10.10.1186/s12575-018-0073-xCrossRefGoogle ScholarPubMed
DePoy, LM, Shapiro, LP, Kietzman, HW, Roman, KM & Gourley, SL (2019). beta1-integrins in the developing orbitofrontal cortex are necessary for expectancy updating in mice. J Neurosci 39(34), 66446655.CrossRefGoogle ScholarPubMed
Eleveld, TF, Schild, L, Koster, J, Zwijnenburg, DA, Alles, LK, Ebus, ME, Volckmann, R, Tijtgat, GA, van Sluis, P, Versteeg, R & Molenaar, JJ (2018). RAS-MAPK pathway-driven tumor progression is associated with loss of CIC and other genomic aberrations in neuroblastoma. Cancer Res 78(21), 62976307.10.1158/0008-5472.CAN-18-1045CrossRefGoogle ScholarPubMed
Eliceiri, BP & Cheresh, DA (1999). The role of alphav integrins during angiogenesis: Insights into potential mechanisms of action and clinical development. J Clin Invest 103(9), 12271230.10.1172/JCI6869CrossRefGoogle ScholarPubMed
Ferreira, M, Fujiwara, H, Morita, K & Watt, FM (2009). An activating beta1 integrin mutation increases the conversion of benign to malignant skin tumors. Cancer Res 69(4), 13341342.10.1158/0008-5472.CAN-08-3051CrossRefGoogle ScholarPubMed
Foubert, P & Varner, JA (2012). Integrins in tumor angiogenesis and lymphangiogenesis. Methods Mol Biol 757, 471486.10.1007/978-1-61779-166-6_27CrossRefGoogle ScholarPubMed
Friedl, P, Wolf, K & Lammerding, J (2011). Nuclear mechanics during cell migration. Curr Opin Cell Biol 23(1), 5564.10.1016/j.ceb.2010.10.015CrossRefGoogle ScholarPubMed
Hynes, RO (1992). Integrins: Versatility, modulation, and signaling in cell adhesion. Cell 69(1), 1125.10.1016/0092-8674(92)90115-SCrossRefGoogle ScholarPubMed
Hynes, RO (2002). Integrins: Bidirectional, allosteric signaling machines. Cell 110, 673687.CrossRefGoogle ScholarPubMed
Kawahara, R, Niwa, Y & Simizu, S (2018). Integrin beta1 is an essential factor in vasculogenic mimicry of human cancer cells. Cancer Sci 109(8), 24902496.10.1111/cas.13693CrossRefGoogle ScholarPubMed
Lundell, BI, McCarthy, JB, Kovach, NL & Verfaillie, CM (1997). Activation of beta1 integrins on CML progenitors reveals cooperation between beta1 integrins and CD44 in the regulation of adhesion and proliferation. Leukemia 11(6), 822829.10.1038/sj.leu.2400653CrossRefGoogle ScholarPubMed
Munger, JS, Huang, X, Kawakatsu, H, Griffiths, MJ, Dalton, SL, Wu, J, Pittet, JF, Kaminski, N, Garat, C, Matthay, MA, Rifkin, DB & Sheppard, D (1999). The integrin alpha v beta 6 binds and activates latent TGF beta 1: A mechanism for regulating pulmonary inflammation and fibrosis. Cell 96(3), 319328.10.1016/S0092-8674(00)80545-0CrossRefGoogle ScholarPubMed
Navab, R, Strumpf, D, To, C, Pasko, E, Kim, KS, Park, CJ, Hai, J, Liu, J, Jonkman, J, Barczyk, M, Bandarchi, B, Wang, YH, Venkat, K, Ibrahimov, E, Pham, NA, Ng, C, Radulovich, N, Zhu, CQ, Pintilie, M, Wang, D, Lu, A, Jurisica, I, Walker, GC, Gullberg, D & Tsao, MS (2016). Integrin alpha11beta1 regulates cancer stromal stiffness and promotes tumorigenicity and metastasis in non-small cell lung cancer. Oncogene 35(15), 18991908.CrossRefGoogle ScholarPubMed
Principe, M, Borgoni, S, Cascione, M, Chattaragada, MS, Ferri-Borgogno, S, Capello, M, Bulfamante, S, Chapelle, J, Di Modugno, F, Defilippi, P, Nisticò, P, Cappello, P, Riganti, C, Leporatti, S & Novelli, F (2017). Alpha-enolase (ENO1) controls alpha v/beta 3 integrin expression and regulates pancreatic cancer adhesion, invasion, and metastasis. J Hematol Oncol 10(1), 16.10.1186/s13045-016-0385-8CrossRefGoogle ScholarPubMed
Qin, L, Chen, X, Wu, Y, Feng, Z, He, T, Wang, L, Liao, L & Xu, J (2011). Steroid receptor coactivator-1 upregulates integrin α5 expression to promote breast cancer cell adhesion and migration. Cancer Res 71(5), 17421751.10.1158/0008-5472.CAN-10-3453CrossRefGoogle ScholarPubMed
Santala, P, Larjava, H, Nissinen, L, Riikonen, T, Määttä, A & Heino, J (1994). Suppressed collagen gene expression and induction of alpha 2 beta 1 integrin-type collagen receptor in tumorigenic derivatives of human osteogenic sarcoma (HOS) cell line. J Biol Chem 269(2), 12761283.10.1016/S0021-9258(17)42254-XCrossRefGoogle Scholar
Schmid, RS & Anton, ES (2003). Role of integrins in the development of the cerebral cortex. Cereb Cortex 13(3), 219224.10.1093/cercor/13.3.219CrossRefGoogle ScholarPubMed
Shain, KH, Yarde, DN, Meads, MB, Huang, M, Jove, R, Hazlehurst, LA & Dalton, WS (2009). Beta1 integrin adhesion enhances IL-6-mediated STAT3 signaling in myeloma cells: Implications for microenvironment influence on tumor survival and proliferation. Cancer Res 69(3), 10091015.CrossRefGoogle ScholarPubMed
Su, YL, Luo, HL, Huang, CC, Liu, TT, Huang, EY, Sung, MT, Lin, JJ, Chiang, PH, Chen, YT, Kang, CH & Cheng, YT (2020). Galectin-1 overexpression activates the FAK/PI3K/AKT/mTOR pathway and is correlated with upper urinary urothelial carcinoma progression and survival. Cells 9(4), 806.10.3390/cells9040806CrossRefGoogle ScholarPubMed
Takasaka, N, Seed, RI, Cormier, A, Bondesson, AJ, Lou, J, Elattma, A, Ito, S, Yanagisawa, H, Hashimoto, M, Ma, R, Levine, MD, Publicover, J, Potts, R, Jespersen, JM, Campbell, MG, Conrad, F, Marks, JD, Cheng, Y, Baron, JL & Nishimura, SL (2018). Integrin αvβ8-expressing tumor cells evade host immunity by regulating TGF-β activation in immune cells. JCI Insight 3(20), e122591.CrossRefGoogle ScholarPubMed
Viquez, OM, Yazlovitskaya, EM, Tu, T, Mernaugh, G, Secades, P, McKee, KK, Georges-Labouesse, E, De Arcangelis, A, Quaranta, V, Yurchenco, P, Gewin, LC, Sonnenberg, A, Pozzi, A & Zent, R (2017). Integrin alpha6 maintains the structural integrity of the kidney collecting system. Matrix Biol 57–58, 244257.CrossRefGoogle ScholarPubMed
Wu, L, Bernard-Trifilo, JA, Lim, Y, Lim, ST, Mitra, SK, Uryu, S, Chen, M, Pallen, CJ, Cheung, NK, Mikolon, D, Mielgo, A, Stupack, DG & Schlaepfer, DD (2008). Distinct FAK-Src activation events promote alpha5beta1 and alpha4beta1 integrin-stimulated neuroblastoma cell motility. Oncogene 27(10), 14391448.10.1038/sj.onc.1210770CrossRefGoogle ScholarPubMed
Xiao, L, Hou, Y, He, H, Cheng, S, Hou, Y, Jin, H, Song, X, Nie, G & Hou, Y (2020). A novel targeted delivery system for drug-resistant hepatocellularcarcinoma therapy. Nanoscale 12(32), 1702917044.10.1039/D0NR01908ACrossRefGoogle Scholar
Xu, Z, Zou, L, Ma, G, Wu, X, Huang, F, Feng, T, Li, S, Lin, Q, He, X, Liu, Z & Cao, X (2017). Integrin β1 is a critical effector in promoting metastasis and chemo-resistance of esophageal squamous cell carcinoma. Am J Cancer Res 7(3), 531542.Google ScholarPubMed
Yusefi, AR, Bagheri Lankarani, K, Bastani, P, Radinmanesh, M & Kavosi, Z (2018). Risk factors for gastric cancer: A systematic review. Asian Pac J Cancer Prev 19(3), 591603.Google ScholarPubMed
Zhu, J, Carman, CV, Kim, M, Shimaoka, M, Springer, TA & Luo, BH (2007). Requirement of α and β subunit transmembrane helix separation for integrin outside-in signaling. Blood 110(7), 24752483.CrossRefGoogle ScholarPubMed

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

ITGB1 Enhances the Proliferation, Survival, and Motility in Gastric Cancer Cells
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

ITGB1 Enhances the Proliferation, Survival, and Motility in Gastric Cancer Cells
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

ITGB1 Enhances the Proliferation, Survival, and Motility in Gastric Cancer Cells
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *