Transforming Growth Factor-β Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2-Dependent Bladder Cancer Cell Migration and Invasion.

Transforming Growth Factor-β Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2-Dependent Bladder Cancer Cell Migration and Invasion. Am J Pathol. 2016 Mar 14; Authors: Gupta S, Hau AM, Al-Ahmadie HA, Harwalkar J, Shoskes AC, Elson P, Beach JR, Hussey GS, Schiemann WP, Egelhoff TT, Howe PH, Hansel DE Abstract Our prior work identified the mammalian target of rapamycin complex 2 (mTORC2) as a key regulator of bladder cancer cell migration and invasion, although upstream growth factor mediators of this pathway in bladder cancer have not been well delineated. We tested whether transforming growth factor (TGF)-β, which can function as a promotility factor in bladder cancer cells, could regulate mTORC2-dependent bladder cancer cell motility and invasion. In human bladder cancers, the highest levels of phosphorylated SMAD2, a TGF-β signaling intermediate, were present in high-grade invasive bladder cancers and associated with more frequent recurrence and decreased disease-specific survival. Increased expression of TGF-β isoforms, receptors, and signaling components was detected in invasive high-grade bladder cancer cells that expressed vimentin and lacked E-cadherin. Application of TGF-β induced phosphorylation of the Ser473 residue of AKT, a selective target of mTORC2, in a Smad2- and Smad4-independent manner and increased bladder cancer cell migration in a modified scratch wound assay and invasion through Matrigel. ...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research