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

Oncotarget
Long ChenShile Huang

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...Continue Reading

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Citations

Jul 7, 2017·Genes & Cancer·Tao ShenShile Huang
Aug 4, 2018·Frontiers in Molecular Biosciences·Marcelle C RibeiroAna Acacia S Pinheiro
Jul 20, 2019·Journal of Cell Communication and Signaling·Shankargouda PatilMarco Ferrari
Oct 10, 2020·Journal of Cell Science·Stephen F SmithPascale G Charest

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Methods Mentioned

BETA
pull-down
GTPases
Assay

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