Oncotarget

Research Papers:

BRSK2 induced by nutrient deprivation promotes Akt activity in pancreatic cancer via downregulation of mTOR activity

Hexige Saiyin, Ning Na, Xu Han, Yuan Fang, Yanhua Wu, Wenhui Lou and Xianmei Yang _

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Oncotarget. 2017; 8:44669-44681. https://doi.org/10.18632/oncotarget.17965

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Abstract

Hexige Saiyin1,*, Ning Na2,*, Xu Han3, Yuan Fang3, Yanhua Wu1, Wenhui Lou3 and Xianmei Yang1

1State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, People’s Republic of China

2Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China

3General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai 20032, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Xianmei Yang, email: [email protected]

Wenhui Lou, email: [email protected]

Keywords: BRSK2, PDAC, Akt, mTOR, AMPK

Received: October 09, 2016     Accepted: April 26, 2017     Published: May 18, 2017

ABSTRACT

Neoplastic cells in pancreatic ductual adenocarcinoma (PDAC) survive in an energy-deprived milieu, and hyper-activation of Akt is thought to contribute to the neoplastic cell survival in PDAC. Kras activating mutations, common in PDAC, was believed to be the major driver of Akt activation. However, the inhibitor to Kras was not therapeutic for PDAC patients. This implied that PDAC cells might harbor an intrinsic merit that strengthens Akt activity. Here we showed that BRSK2, a serine/threonine-protein kinase of AMPK family, was induced by nutrient deprivation in PDAC cells and suppressed mTORC1 activity via phosphorylation of tuberous sclerosis complex 2 (TSC2). The suppression of mTORC1 activity in PDAC results in a dominant loss of feedback inhibition on Akt activity by mTORC1, consequently enhancing cell survival. This finding indicates that the intrinsic molecular merit that BRSK2 provides is a survival advantage to PDAC cells and strengthens the invasiveness of these neoplastic cells in energy-deprived environments.


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