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

Guixi Zheng, Hakim Bouamar, Matyas Cserhati, Carla R. Zeballos, Isha Mehta, Habil Zare, Larry Broome, Ruolei Hu, Zhao Lai, Yidong Chen, Francis E. Sharkey, Meenakshi Rani, Glenn A. Halff, Francisco G. Cigarroa, Lu Zhe Sun

Resultado de la investigación: Articlerevisión exhaustiva


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.

Idioma originalEnglish (US)
Páginas (desde-hasta)930-943
Número de páginas14
PublicaciónInternational Journal of Cancer
EstadoPublished - sept 15 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Profundice en los temas de investigación de 'Integrin alpha 6 is upregulated and drives hepatocellular carcinoma progression through integrin α6β4 complex'. En conjunto forman una huella única.

Citar esto