SCIENCE@home

Prevention of epithelial to mesenchymal transition in colorectal carcinoma by regulation of the E-cadherin-β-catenin-vinculin axis.

I. Pal,I. Pal,Y. Rajesh,Payel Banik,G. Dey,K. Dey,R. Bharti,D. Naskar,S. Chakraborty,S. Ghosh,Swadesh K. Das,L. Emdad,Subhas C. Kundu,Subhas C. Kundu,P. Fisher,M. Mandal

Published 2019 in Cancer Letters

ABSTRACT

Epithelial to mesenchymal transition (EMT) is compulsory for metastatic dissemination and is stimulated by TGF-β. Although targeting EMT has significant therapeutic potential, very few pharmacological agents have been shown to exert anti-metastatic effects. BI-69A11, a competitive Akt inhibitor, displays anti-tumor activity toward melanoma and colon carcinoma. This study provides molecular and biochemical insights into the effects of BI-69A11 on EMT in colon carcinoma cells in vitro and in vivo. BI-69A11 inhibited metastasis-associated cellular migration, invasion and adhesion by inhibiting the Akt-β-catenin pathway. The underlying mechanism of BI-69A11-mediated inhibition of EMT included suppression of nuclear transport of β-catenin and diminished phosphorylation of β-catenin, which was accompanied by enhanced E-cadherin-β-catenin complex formation at the plasma membrane. Additionally, BI-69A11 caused increased accumulation of vinculin in the plasma membrane, which fortified focal adhesion junctions leading to inhibition of metastasis. BI-69A11 downregulated activation of the TGF-β-induced non-canonical Akt/NF-κB pathway and blocked TGF-β-induced enhanced expression of Snail causing restoration of E-cadherin. Overall, this study enhances our understanding of the molecular mechanism of BI-69A11-induced reversal of EMT in colorectal carcinoma cells in vitro, in vivo and in TGF-β-induced model systems.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-60 of 60 references · Page 1 of 1

CITED BY

Showing 1-37 of 37 citing papers · Page 1 of 1