Oncotarget

Research Papers:

Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion

Long Chen _, Baoshan Xu, Lei Liu, Chunxiao Liu, Yan Luo, Xin Chen, Mansoureh Barzegar, Jun Chung and Shile Huang

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Oncotarget. 2015; 6:7136-7150. https://doi.org/10.18632/oncotarget.3044

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Abstract

Long Chen1,2, Baoshan Xu2, Lei Liu2, Chunxiao Liu1, Yan Luo2, Xin Chen2, Mansoureh Barzegar2, Jun Chung2,3, Shile Huang2,3

1Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, P. R. China

2Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA

3Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA

Correspondence to:

Shile Huang, e-mail: shuan1@lsuhsc.edu

Long Chen, e-mail: lchen@njnu.edu.cn

Keywords: rapamycin, mTOR, cell adhesion, Akt, 4E-BP1

Received: September 09, 2014     Accepted: January 07, 2015     Published: January 23, 2015

ABSTRACT

mTOR is a central controller for cell growth/proliferation and survival. Recent studies have shown that mTOR also regulates cell adhesion, yet the underlying mechanism is not known. Here we found that inhibition of mTOR by rapamycin reduced the basal or type I insulin-like growth factor (IGF-1)-stimulated adhesion of cancer cells. Further research revealed that both mTORC1 and mTORC2 were involved in the regulation of cell adhesion, as silencing expression of raptor or rictor inhibited cell adhesion. Also, PP242, an mTORC1/2 kinase inhibitor, inhibited cell adhesion more potently than rapamycin (mTORC1 inhibitor). Of interest, ectopic expression of constitutively active and rapamycin-resistant mutant of p70 kinase 1 (S6K1) or downregulation of eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) conferred resistance to rapamycin inhibition of cell adhesion, whereas expression of constitutively hypophosphorylated 4E-BP1 (4EBP1-5A) or downregulation of S6K1 suppressed cell adhesion. In contrast, neither genetic manipulation of Akt activity nor pharmacological inhibition of Akt affected cell adhesion. The results suggest that both mTORC1 and mTORC2 are involved in the regulation of cell adhesion; and mTORC1 regulates cell adhesion through S6K1 and 4E-BP1 pathways, but mTORC2 regulates cell adhesion via Akt-independent mechanism.


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