Loss of miR-200b promotes invasion via activating the Kindlin-2/integrin β1/AKT pathway in esophageal squamous cell carcinoma: An E-cadherin-independent mechanism

Oncotarget
Hai-Feng ZhangEn-Min Li

Abstract

Our previous studies have shown that loss of miR-200b enhances the invasiveness of esophageal squamous cell carcinoma (ESCC) cells. However, whether the miR-200-ZEB1/2-E-cadherin regulatory cascade, a master regulator of epithelial-to-mesenchymal transition (EMT), is involved in the regulation of ESCC invasion remains elusive. Here, we show that miR-200b represses ESCC cell invasion in vivo without altering the expression of E-cadherin and vimentin, two surrogate markers of EMT. However, an inverse correlation was observed between the expression levels of miR-200b and ZEB1/2 in both ESCC cell lines (n = 7, P < 0.05) and ESCC tumor samples (n = 88, P < 0.05). Methylation of E-cadherin gene was found to block the regulation of E-cadherin by the miR-200b-ZEB1/2 axis, indicating that an E-cadherin-independent mechanism can mediate the biological function of miR-200b in ESCC. We revealed that miR-200b suppresses the integrin β1-AKT pathway via targeting Kindlin-2 to mitigate ESCC cell invasiveness. In two independent cohorts of ESCC samples (n = 20 and n = 53, respectively), Kindlin-2 expression positively correlated with the activation status of both the integrin signaling pathway and the PI3K-AKT signaling pathway (both P < 0.01)....Continue Reading

References

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Citations

Jun 9, 2016·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Shaorong ZhangJingying Liu
May 25, 2016·Cell Proliferation·Blanca Ortiz-Quintero
Sep 22, 2020·Journal of Cellular and Molecular Medicine·Jian-Ling XuHan-Ming Jiang
Nov 24, 2016·International Journal of Oncology·Zhifang GuiJian Xu
Dec 5, 2015·Frontiers in Pharmacology·Anne-Florence BlandinMonique Dontenwill
Oct 4, 2017·Journal of Experimental & Clinical Cancer Research : CR·Jie LinAimin Huang
Apr 4, 2021·International Journal of Molecular Sciences·Giovanni ZarrilliMatteo Fassan

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Methods Mentioned

BETA
xenografts
PCR
transfection
flow cytometry
GTPases
surgical resection
Assay

Software Mentioned

GSEA ( Gene Set Enrichment Analysis )
Graphpad Prism
SPSS

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