Integrin alpha 6 is upregulated and drives hepatocellular carcinoma progression through integrin α6β4 complex.

Autor:	Zheng G; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.; Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong, China., Bouamar H; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Cserhati M; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Zeballos CR; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Mehta I; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Zare H; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Broome L; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Hu R; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Lai Z; Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Chen Y; Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.; Department of Population Health Sciences, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Sharkey FE; Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Rani M; Transplant Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Halff GA; Transplant Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Cigarroa FG; Transplant Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Sun LZ; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Jazyk:	angličtina
Zdroj:	International journal of cancer [Int J Cancer] 2022 Sep 15; Vol. 151 (6), pp. 930-943. Date of Electronic Publication: 2022 Jun 19.
DOI:	10.1002/ijc.34146
Abstrakt:	Integrin α6 (ITGA6) forms integrin receptors with either integrin β1 (ITGB1) or integrin β4 (ITGB4). How it functions to regulate hepatocellular carcinoma (HCC) progression is not well-elucidated. We found that ITGA6 RNA and protein expression levels are significantly elevated in human HCC tissues in comparison with paired adjacent nontumor tissues by RNA sequencing, RT-qPCR, Western blotting and immunofluorescence staining. Stable knockdown of ITGA6 with different ITGA6 shRNA expression lentivectors significantly inhibited proliferation, migration and anchorage-independent growth of HCC cell lines in vitro, and xenograft tumor growth in vivo. The inhibition of anchorage-dependent and -independent growth of HCC cell lines was also confirmed with anti-ITGA6 antibody. ITGA6 knockdown was shown to induce cell-cycle arrest at G0/G1 phase. Immunoprecipitation assay revealed apparent interaction of ITGA6 with ITGB4, but not ITGB1. Expression studies showed that ITGA6 positively regulates the expression of ITGB4 with no or negative regulation of ITGB1 expression. Finally, while high levels of ITGA6 and ITGB4 together were associated with significantly worse survival of HCC patients in TCGA data set, the association was not significant for high levels of ITGA6 and ITGB1. In conclusion, ITGA6 is upregulated in HCC tumors and has a malignant promoting role in HCC cells through integrin α6β4 complex. Thus, integrin α6β4 may be a therapeutic target for treating patients with HCC. (© 2022 UICC.)
Databáze:	MEDLINE
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