NDLI: Distinct Roles for Mammalian Target of Rapamycin Complexes in the Fibroblast Response to Transforming Growth Factor-beta

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Distinct Roles for Mammalian Target of Rapamycin Complexes in the Fibroblast Response to Transforming Growth Factor-beta

Content Provider	PubMed Central
Author	Rahimi, Rod A. Andrianifahanana, Mahefatiana Wilkes, Mark C. Edens, Maryanne Kottom, Theodore J. John, Blenis Leof, Edward B.
Abstract	Transforming growth factor-beta (TGF-β) promotes a multitude of diverse biological processes including growth arrest of epithelial cells and proliferation of fibroblasts. While the TGF-β signaling pathways that promote inhibition of epithelial cell growth are well characterized, less is known regarding the mechanisms mediating the positive response to this growth factor. Given that TGF-β has been demonstrated to promote fibrotic diseases and desmoplasia, identifying the fibroblast-specific TGF-β signaling pathways is critical. Here we investigate the role of mammalian target of rapamycin (mTOR), a known effector of PI3K and promoter of cell growth, in the fibroblast response to TGF-β. We show that TGF-β activates mTORC1 in fibroblasts but not epithelial cells via a PI3K-Akt-TSC2 dependent pathway. Rapamycin, the pharmacological inhibitor of mTOR, prevents TGF-β mediated anchorage-independent growth without affecting TGF-β transcriptional responses or extracellular matrix protein induction. In addition to mTORC1, we also examined the role of mTORC2 in TGF-β action. mTORC2 promotes TGF-β induced morphological transformation and is required for TGF-β induced Akt S473 phosphorylation, but not mTORC1 activation. Interestingly, both mTOR complexes are necessary for TGF-β mediated growth in soft agar. These results define distinct and over-lapping roles for mTORC1 and mTORC2 in the fibroblast response to TGF-β and suggest that inhibitors of mTOR signaling may be useful in treating fibrotic processes such as desmoplasia.
Related Links	http://dx.doi.org/10.1158/0008-5472.CAN-08-2146
Starting Page	84
File Format	PDF
ISSN	15387445
e-ISSN	15387445
Journal	Cancer research
Issue Number	1
Volume Number	69
Language	English
Publisher Date	2009-01-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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