Mammalian target of rapamycin complex 2 (mTORC2) is a critical determinant of bladder cancer invasion

Sounak Gupta, Andrew M. Hau, Jordan R. Beach, Jyoti Harwalker, Elisabetta Mantuano, Steven L. Gonias, Thomas T. Egelhoff, Donna E. Hansel

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Bladder cancer is the fourth most common cause of cancer in males in the United States. Invasive behavior is a major determinant of prognosis. In this study, we identified mammalian target of rapamycin complex 2 (mTORC2) as a central regulator of bladder cancer cell migration and invasion. mTORC2 activity was assessed by the extent of phosphorylation of Ser473 in AKT and determined to be approximately 5-fold higher in specimens of invasive human bladder cancer as opposed to non-invasive human bladder cancer. The immortalized malignant bladder cell lines, UMUC-3, J82 and T24 demonstrated higher baseline mTORC2 activity relative to the benign bladder papillomaderived cell line RT4 and the normal urothelial cell line HU1. The malignant bladder cancer cells also demonstrated increased migration in transwell and denudation assays, increased invasion of matrigel, and increased capacity to invade human bladder specimens. Gene silencing of rictor, a critical component of mTORC2, substantially inhibited bladder cancer cell migration and invasion. This was accompanied by a significant decrease in Rac1 activation and paxillin phosphorylation. These studies identify mTORC2 as a major target for neutralizing bladder cancer invasion.

Original languageEnglish (US)
Article numbere81081
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 27 2013
Externally publishedYes

ASJC Scopus subject areas

  • General

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