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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

ITGA9: Potential Biomarkers and Therapeutic Targets in Different Tumors

Author(s): Yinxin Wu, Jinlan Chen, Fangshun Tan, Bei Wang, Wen Xu and Chengfu Yuan*

Volume 28, Issue 17, 2022

Published on: 27 May, 2022

Page: [1412 - 1418] Pages: 7

DOI: 10.2174/1381612828666220501165644

Price: $65

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Abstract

Integrins are a class of cell surface adhesion molecules composed of α subunit (ITGA) and β subunit (ITGB). They belong to heterodimer transmembrane glycoproteins. Their main function in organisms is as the receptor of cell adhesion molecules (CAMs) and extracellular matrix (ECM). According to the current research integration analysis, integrin α9 (ITGA9) is one of the integrin subunits, and there are few studies on ITGA9 among integrins. ITGA9 can improve cell migration and regulate various cellular biological functions, such as tumor cell proliferation, adhesion, invasion, and angiogenesis. However, its abnormal expression mechanism in cancer and its specific role in tumor growth and metastasis are still unknown to a great extent. This review reveals the role of ITGA9 in the complex pathogenesis of many tumors and cancers, providing a new direction for the treatment of tumors and cancers. Relevant studies were retrieved and collected through the PubMed system. After determining ITGA9 as the research object, we found a close relationship between ITGA9 and tumorigenesis by analyzing the research articles on ITGA9 in the PubMed system in the last 15 years and further determined the references mainly based on the influencing factors of the articles. Thus, the role of ITGA9 in tumor and cancer genesis, proliferation, and metastasis was reviewed and analyzed. ITGA9 is an integrin subunit, which has been proved to be abnormally expressed in many tumors. After sorting and analyzing the research data, it was found that the abnormal expression of ITGA9 in a variety of tumors, including glioblastoma, rhabdomyosarcoma, melanoma, hepatocellular carcinoma, nasopharyngeal carcinoma, multiple myeloma, non-small cell lung cancer, and prostate cancer, was closely related to the proliferation, metastasis, adhesion, and angiogenesis of tumor cells. These results suggest that ITGA9 plays an important role in the occurrence and development of tumors. The integrin subunit ITGA9 may serve as a biomarker for the diagnosis of tumors and a potential therapeutic target for anti-tumor therapies.

Keywords: Integrin subunits, ITGA9, cancer, mechanisms, biomarkers, targets.

« Previous Next »
[1]
Li ZH, Zhou Y, Ding YX, Guo QL, Zhao L. Roles of integrin in tumor development and the target inhibitors. Chin J Nat Med 2019; 17(4): 241-51.
[http://dx.doi.org/10.1016/S1875-5364(19)30028-7] [PMID: 31076128]
[2]
Høye AM, Couchman JR, Wewer UM, Fukami K, Yoneda A. The newcomer in the integrin family: Integrin α9 in biology and cancer. Adv Biol Regul 2012; 52(2): 326-39.
[http://dx.doi.org/10.1016/j.jbior.2012.03.004] [PMID: 22781746]
[3]
Chen C, Kudo M, Rutaganira F, et al. Integrin α9β1 in airway smooth muscle suppresses exaggerated airway narrowing. J Clin Invest 2012; 122(8): 2916-27.
[http://dx.doi.org/10.1172/JCI60387] [PMID: 22772469]
[4]
Xu TJ, Qiu P, Zhang YB, Yu SY, Xu GM, Yang W. miR-148a inhibits the proliferation and migration of glioblastoma by targeting ITGA9. Hum Cell 2019; 32(4): 548-56.
[http://dx.doi.org/10.1007/s13577-019-00279-9] [PMID: 31489579]
[5]
Molist C, Navarro N, Giralt I, et al. miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma. Cancer Lett 2020; 477: 49-59.
[http://dx.doi.org/10.1016/j.canlet.2020.02.035] [PMID: 32142919]
[6]
Xu Y, Zhang J, Zhang Q, Xu H, Liu L. Long non-coding RNA HOXA11-AS modulates proliferation, apoptosis, metastasis and EMT in cutaneous melanoma cells partly. via miR-152-3p/ITGA9 axis. Cancer Manag Res 2021; 13: 925-39.
[http://dx.doi.org/10.2147/CMAR.S281920] [PMID: 33564267]
[7]
Zhang J, Na S, Liu C, Pan S, Cai J, Qiu J. MicroRNA-125b suppresses the epithelial-mesenchymal transition and cell invasion by targeting ITGA9 in melanoma. Tumour Biol 2016; 37(5): 5941-9.
[http://dx.doi.org/10.1007/s13277-015-4409-8] [PMID: 26596831]
[8]
Fan J, Kang X, Zhao L, et al. Long noncoding RNA CCAT1 functions as a competing endogenous RNA to upregulate ITGA9 by sponging miR-296-3p in melanoma. Cancer Manag Res 2020; 12: 4699-714.
[http://dx.doi.org/10.2147/CMAR.S252635] [PMID: 32606961]
[9]
Wang Z, Li Y, Xiao Y, et al. Integrin α9 depletion promotes β-catenin degradation to suppress triple-negative breast cancer tumor growth and metastasis. Int J Cancer 2019; 145(10): 2767-80.
[http://dx.doi.org/10.1002/ijc.32359] [PMID: 31008533]
[10]
Zhang YL, Xing X, Cai LB, et al. Integrin α9 suppresses hepatocellular carcinoma metastasis by Rho GTPase signaling. J Immunol Res 2018; 2018: 4602570.
[http://dx.doi.org/10.1155/2018/4602570] [PMID: 29951557]
[11]
Liu L, Wang H, Yan C, Tao S. An integrated analysis of mRNAs and miRNAs microarray profiles to screen miRNA signatures involved in nasopharyngeal carcinoma. Technol Cancer Res Treat 2020; 19: 1533033820956998.
[http://dx.doi.org/10.1177/1533033820956998] [PMID: 32985354]
[12]
Nawaz I, Moumad K, Martorelli D, et al. Detection of nasopharyngeal carcinoma in Morocco (North Africa) using a multiplex methylation-specific PCR biomarker assay. Clin Epigenetics 2015; 7(1): 89.
[http://dx.doi.org/10.1186/s13148-015-0119-8] [PMID: 26300994]
[13]
Nawaz I, Hu LF, Du ZM, et al. Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma. Oncotarget 2015; 6(31): 31493-507.
[http://dx.doi.org/10.18632/oncotarget.5154] [PMID: 26372814]
[14]
Peng Y, Wu D, Li F, Zhang P, Feng Y, He A. Identification of key biomarkers associated with cell adhesion in multiple myeloma by integrated bioinformatics analysis. Cancer Cell Int 2020; 20(1): 262.
[http://dx.doi.org/10.1186/s12935-020-01355-z] [PMID: 32581652]
[15]
Anedchenko EA, Dmitriev AA, Krasnov GS, et al. Downregulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1, and HYAL2 in non-small cell lung cancer. Mol Biol 2008; 42(6): 859-69.
[http://dx.doi.org/10.1134/S0026893308060058]
[16]
Pastuszak-Lewandoska D, Kordiak J, Antczak A, et al. Expression level and methylation status of three tumor suppressor genes, DLEC1, ITGA9 and MLH1, in non-small cell lung cancer. Med Oncol 2016; 33(7): 75.
[http://dx.doi.org/10.1007/s12032-016-0791-3] [PMID: 27287342]
[17]
Dmitriev AA, Rosenberg EE, Krasnov GS, et al. Identification of novel epigenetic markers of prostate cancer by noti-microarray analysis. Dis Markers 2015; 2015: 241301.
[http://dx.doi.org/10.1155/2015/241301] [PMID: 26491211]
[18]
Jiapaer S, Furuta T, Tanaka S, Kitabayashi T, Nakada M. Potential strategies overcoming the temozolomide resistance for glioblastoma. Neurol Med Chir 2018; 58(10): 405-21.
[http://dx.doi.org/10.2176/nmc.ra.2018-0141] [PMID: 30249919]
[19]
Shen J, Stass SA, Jiang F. MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett 2013; 329(2): 125-36.
[http://dx.doi.org/10.1016/j.canlet.2012.11.001] [PMID: 23196059]
[20]
Perkins SM, Shinohara ET, DeWees T, Frangoul H. Outcome for children with metastatic solid tumors over the last four decades. PLoS One 2014; 9(7): e100396.
[http://dx.doi.org/10.1371/journal.pone.0100396] [PMID: 25003594]
[21]
Zhao J, Tao Y, Zhou Y, et al. MicroRNA-7: A promising new target in cancer therapy. Cancer Cell Int 2015; 15(1): 103.
[http://dx.doi.org/10.1186/s12935-015-0259-0] [PMID: 26516313]
[22]
Strelnikov VV, Kuznetsova EB, Tanas AS, et al. Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer. Sci Rep 2021; 11(1): 2264.
[http://dx.doi.org/10.1038/s41598-021-81851-y] [PMID: 33500458]
[23]
Babae N, Bourajjaj M, Liu Y, et al. Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma. Oncotarget 2014; 5(16): 6687-700.
[http://dx.doi.org/10.18632/oncotarget.2235] [PMID: 25149532]
[24]
Ferretti E, De Smaele E, Miele E, et al. Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J 2008; 27(19): 2616-27.
[http://dx.doi.org/10.1038/emboj.2008.172] [PMID: 18756266]
[25]
Tang B, Xu A, Xu J, et al. MicroRNA-324-5p regulates stemness, pathogenesis and sensitivity to bortezomib in multiple myeloma cells by targeting hedgehog signaling. Int J Cancer 2018; 142(1): 109-20.
[http://dx.doi.org/10.1002/ijc.31041] [PMID: 28905994]
[26]
Berrocal A, Cabañas L, Espinosa E, et al. Melanoma: Diagnosis, staging, and treatment. Consensus group recommendations. Adv Ther 2014; 31(9): 945-60.
[http://dx.doi.org/10.1007/s12325-014-0148-2] [PMID: 25145549]
[27]
Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: Mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta 2009; 1796(2): 75-90.
[PMID: 19306912]
[28]
Mostovich LA, Prudnikova TY, Kondratov AG, et al. Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors. Cell Adhes Migr 2011; 5(5): 395-401.
[http://dx.doi.org/10.4161/cam.5.5.17949] [PMID: 21975548]
[29]
Gupta SK, Oommen S, Aubry MC, Williams BP, Vlahakis NE. Integrin α9β1 promotes malignant tumor growth and metastasis by potentiating epithelial-mesenchymal transition. Oncogene 2013; 32(2): 141-50.
[http://dx.doi.org/10.1038/onc.2012.41] [PMID: 22370635]
[30]
Sinha S, Singh RK, Alam N, Roy A, Roychoudhury S, Panda CK. Frequent alterations of hMLH1 and RBSP3/HYA22 at chromosomal 3p22.3 region in early and late-onset breast carcinoma: Clinical and prognostic significance. Cancer Sci 2008; 99(10): 1984-91.
[PMID: 19016758]
[31]
Kast K, Link T, Friedrich K, et al. Impact of breast cancer subtypes and patterns of metastasis on outcome. Breast Cancer Res Treat 2015; 150(3): 621-9.
[http://dx.doi.org/10.1007/s10549-015-3341-3] [PMID: 25783184]
[32]
Nusse R, Clevers H. Wnt/β-Catenin signaling, disease, and emerging therapeutic modalities. Cell 2017; 169(6): 985-99.
[http://dx.doi.org/10.1016/j.cell.2017.05.016] [PMID: 28575679]
[33]
Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene 2017; 36(11): 1461-73.
[http://dx.doi.org/10.1038/onc.2016.304] [PMID: 27617575]
[34]
Liu CY, Chen KF, Chen PJ. Treatment of liver cancer. Cold Spring Harb Perspect Med 2015; 5(9): a021535.
[http://dx.doi.org/10.1101/cshperspect.a021535] [PMID: 26187874]
[35]
Bissell MJ, Hines WC. Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 2011; 17(3): 320-9.
[http://dx.doi.org/10.1038/nm.2328] [PMID: 21383745]
[36]
Zhang YL, Li Q, Yang XM, et al. SPON2 Promotes M1-like macrophage recruitment and inhibits hepatocellular carcinoma metastasis by distinct integrin-Rho GTPase-hippo pathways. Cancer Res 2018; 78(9): 2305-17.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-2867] [PMID: 29440144]
[37]
Mitra SK, Schlaepfer DD. Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 2006; 18(5): 516-23.
[http://dx.doi.org/10.1016/j.ceb.2006.08.011] [PMID: 16919435]
[38]
Ng CC, Yew PY, Puah SM, et al. A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma. J Hum Genet 2009; 54(7): 392-7.
[http://dx.doi.org/10.1038/jhg.2009.49] [PMID: 19478819]
[39]
Lo KW, Chung GT, To KF. Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol 2012; 22(2): 79-86.
[http://dx.doi.org/10.1016/j.semcancer.2011.12.011] [PMID: 22245473]
[40]
Robak P, Drozdz I, Szemraj J, Robak T. Drug resistance in multiple myeloma. Cancer Treat Rev 2018; 70: 199-208.
[http://dx.doi.org/10.1016/j.ctrv.2018.09.001] [PMID: 30245231]
[41]
Leleu X. New hope for relapsed and refractory multiple myeloma. Lancet Oncol 2013; 14(11): 1028-9.
[http://dx.doi.org/10.1016/S1470-2045(13)70399-1] [PMID: 24007745]
[42]
Neri P, Bahlis NJ. Targeting of adhesion molecules as a therapeutic strategy in multiple myeloma. Curr Cancer Drug Targets 2012; 12(7): 776-96.
[http://dx.doi.org/10.2174/156800912802429337] [PMID: 22671924]
[43]
Katz BZ. Adhesion molecules--The lifelines of multiple myeloma cells. Semin Cancer Biol 2010; 20(3): 186-95.
[http://dx.doi.org/10.1016/j.semcancer.2010.04.003] [PMID: 20416379]
[44]
Evison M. AstraZeneca UK Limited. The current treatment landscape in the UK for stage III NSCLC. Br J Cancer 2020; 123(S1)(Suppl. 1): 3-9.
[http://dx.doi.org/10.1038/s41416-020-01069-z] [PMID: 33293670]
[45]
Esteller M. Epigenetics in cancer. N Engl J Med 2008; 358(11): 1148-59.
[http://dx.doi.org/10.1056/NEJMra072067] [PMID: 18337604]
[46]
Dmitriev AA, Kashuba VI, Haraldson K, et al. Genetic and epigenetic analysis of non-small cell lung cancer with NOTI-microarrays. Epigenetics 2012; 7(5): 502-13.
[http://dx.doi.org/10.4161/epi.19801] [PMID: 22491060]
[47]
Anedchenko EA, Dmitriev AA, Krasnov GS, et al. Down-regulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 genes in non-small cell lung cancer. Mol Biol 2008; 42(6): 965-76.
[PMID: 19140316]
[48]
Leece R, Xu J, Ostrom QT, Chen Y, Kruchko C, Barnholtz-Sloan JS. Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007. Neuro-oncol 2017; 19(11): 1553-64.
[http://dx.doi.org/10.1093/neuonc/nox091] [PMID: 28482030]
[49]
Katsogiannou M, Ziouziou H, Karaki S, Andrieu C, Henry de Villeneuve M, Rocchi P. The hallmarks of castration-resistant prostate cancers. Cancer Treat Rev 2015; 41(7): 588-97.
[http://dx.doi.org/10.1016/j.ctrv.2015.05.003] [PMID: 25981454]
[50]
Sandoval J, Peiró-Chova L, Pallardó FV, García-Giménez JL. Epigenetic biomarkers in laboratory diagnostics: Emerging approaches and opportunities. Expert Rev Mol Diagn 2013; 13(5): 457-71.
[http://dx.doi.org/10.1586/erm.13.37] [PMID: 23782253]
[51]
Pan J, Chen Y, Mo C, et al. Association of DSC3 mRNA down-regulation in prostate cancer with promoter hypermethylation and poor prognosis. PLoS One 2014; 9(3): e92815.
[http://dx.doi.org/10.1371/journal.pone.0092815] [PMID: 24664224]

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