Krebswissenschaft und -therapie

MTA1 Aids the AKT Pathway by Inhibiting Expression of a Key Regulator, PTEN

Abstract

Shimul Salot and Rajiv Gude

Metastasis is the final result of actions of various genes, one of which is the Metastasis Associated 1 (MTA1) gene. MTA1 acts as part of a nucleosome remodeling and histone deacetylation complex and has been shown to aid metastasis by regulating many other molecules. We decided to study if there was any possible relationship between MTA1 and the phosphatase and tensin analogue mutated on chromosome 10 (PTEN). PTEN is a tumour suppressor gene known to be mutated in several cancers. We found that on knockdown of MTA1 using siRNA, PTEN protein levels increased albeit its mRNA levels were unchanged. We further found that MTA1 and PTEN colocalize and coimmunoprecipitate with each other. PTEN levels increased on inhibiting histone deacetyalse activity, such as possessed by MTA1. One of the most celebrated functions of PTEN is its regulation of the PI3K-Akt pathway. We found that the levels of active AKT decreased in cells treated with siRNA against MTA1. We hypothesize that MTA1 helps in maintaining the AKT pathway in cancer cells by inhibiting PTEN, a major antagonist of the pathway. This might be one of the several mechanisms by which MTA1 aids metastasis.