Dissecting the signaling pathways that mediate cancer in PTEN and LKB1 double-knockout mice.

Abstract:

:Double knockout of PTEN and LKB1-genes encoding phosphatase and tensin homolog and liver kinase B1, respectively-leads to the spontaneous development of cancer in mice. PTEN converts phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to phosphatidylinositol (4,5)-bisphosphate (PIP2), whereas LKB1 activates the 5' adenosine monophosphate-activated protein kinase (AMPK). The kinase AKT and the kinase complex mTORC1 may play key roles in carcinogenesis and are components of signaling pathways that also contain PTEN and LKB1. We propose that via activation of AKT and mTORC1, the double knockout of PTEN and LKB1 contributes to distinct cell-specific aspects of tumor development and progression. Whereas mTORC1 promotes cancer initiation and progression through cell growth, survival, and proliferation, independent induction of the immune inhibitory molecule PD-L1 by activated AKT enables the tumors to evade immunosurveillance.

journal_name

Sci Signal

journal_title

Science signaling

authors

Chen J,Zhang XD,Proud C

doi

10.1126/scisignal.aac8321

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

pe1

issue

392

eissn

1945-0877

issn

1937-9145

pii

8/392/pe1

journal_volume

8

pub_type

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