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

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)-stim...

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Main Authors:	Chen, Long, Xu, Baoshan, Liu, Lei, Liu, Chunxiao, Luo, Yan, Chen, Xin, Barzegar, Mansoureh, Chung, Jun, Huang, Shile
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466674/

id	pubmed-4466674
recordtype	oai_dc
spelling	pubmed-44666742015-06-22 Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion Chen, Long Xu, Baoshan Liu, Lei Liu, Chunxiao Luo, Yan Chen, Xin Barzegar, Mansoureh Chung, Jun Huang, Shile Research Paper 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. Impact Journals LLC 2015-01-23 /pmc/articles/PMC4466674/ /pubmed/25762619 Text en Copyright: © 2015 Chen et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chen, Long Xu, Baoshan Liu, Lei Liu, Chunxiao Luo, Yan Chen, Xin Barzegar, Mansoureh Chung, Jun Huang, Shile
spellingShingle	Chen, Long Xu, Baoshan Liu, Lei Liu, Chunxiao Luo, Yan Chen, Xin Barzegar, Mansoureh Chung, Jun Huang, Shile Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion
author_facet	Chen, Long Xu, Baoshan Liu, Lei Liu, Chunxiao Luo, Yan Chen, Xin Barzegar, Mansoureh Chung, Jun Huang, Shile
author_sort	Chen, Long
title	Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion
title_short	Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion
title_full	Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion
title_fullStr	Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion
title_full_unstemmed	Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion
title_sort	both mtorc1 and mtorc2 are involved in the regulation of cell adhesion
description	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.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466674/
_version_	1613235500624117760

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

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