TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade.

Abstract:

:Aberrant activation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss or inactivation of TSC1/TSC2 protein complex, leads to negative feedback inhibition of Akt. The exact mechanisms of this process are still not fully understood. Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process. We demonstrate that STAT3 promotes the transcription of PTEN by directly binding on the PTEN promoter. Elevated PTEN then inhibits the proliferation of Tsc1(-/-) or Tsc2(-/-) cells through down-regulation of Akt signaling. Activation of PTEN in this pathway may thus serve as a protective mechanism against hyper-activated mTORC1 mediated tumorigenesis and contribute to the benign nature of tumors caused by loss of either TSC1 or TSC2.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Zha X,Hu Z,He S,Wang F,Shen H,Zhang H

doi

10.1016/j.canlet.2011.09.006

subject

Has Abstract

pub_date

2011-12-27 00:00:00

pages

211-7

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(11)00536-2

journal_volume

313

pub_type

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