TY - JOUR
T1 - An evolving role for DEPTOR in tumor development and progression
AU - Wang, Zhiwei
AU - Zhong, Jiateng
AU - Inuzuka, Hiroyuki
AU - Gao, Daming
AU - Shaik, Shavali
AU - Sarkar, Fazlul H.
AU - Wei, Wenyi
N1 - Funding Information:
Address all correspondence to: Wenyi Wei, PhD, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215. E-mail: wwei2@bidmc.harvard.edu 1This work was supported by grants from the National Institute of General Medicines, National Institutes of Health (NIH; GM089763 and GM094777 to W.W.). 2Z. W. is supported by an NIH National Research Service Award fellowship. 3W. W. is an American Cancer Society Scholar. Received 19 March 2012; Revised 5 April 2012; Accepted 9 April 2012 Copyright © 2012 Neoplasia Press, Inc. All rights reserved 1522-8002/12/$25.00 DOI 10.1593/neo.12542
PY - 2012/5
Y1 - 2012/5
N2 - Deregulation of the mammalian target of rapamycin (mTOR) signaling pathway has been found in a variety of human cancers. However, the exact molecular mechanism how the mTOR signaling pathway is regulated remains largely elusive. Recently, DEPTOR was identified as an endogenous mTOR inhibitor that could suppress mTOR activity in vivo. More importantly, accumulated evidence has implicated that DEPTOR plays a pivotal role in the development and progression of human malignances, which could in part be mediated through its inhibitory role toward mTOR. Furthermore, three independent laboratories including our own have demonstrated that the stability of DEPTOR is controlled by the SCFβ-TrCP E3 ubiquitin ligase and deregulated DEPTOR destruction might contribute to hyperactivation of mTOR in pathologic conditions including cancer. This review discusses the recent literature regarding the function of DEPTOR involved in cell growth, apoptosis, autophagy, epithelial-mesenchymal transition, and drug resistance, all of which are associated with the pathogenesis of human cancers. Moreover, we also summarize that targeting DEPTOR may be a novel strategy for achieving better anticancer treatments.
AB - Deregulation of the mammalian target of rapamycin (mTOR) signaling pathway has been found in a variety of human cancers. However, the exact molecular mechanism how the mTOR signaling pathway is regulated remains largely elusive. Recently, DEPTOR was identified as an endogenous mTOR inhibitor that could suppress mTOR activity in vivo. More importantly, accumulated evidence has implicated that DEPTOR plays a pivotal role in the development and progression of human malignances, which could in part be mediated through its inhibitory role toward mTOR. Furthermore, three independent laboratories including our own have demonstrated that the stability of DEPTOR is controlled by the SCFβ-TrCP E3 ubiquitin ligase and deregulated DEPTOR destruction might contribute to hyperactivation of mTOR in pathologic conditions including cancer. This review discusses the recent literature regarding the function of DEPTOR involved in cell growth, apoptosis, autophagy, epithelial-mesenchymal transition, and drug resistance, all of which are associated with the pathogenesis of human cancers. Moreover, we also summarize that targeting DEPTOR may be a novel strategy for achieving better anticancer treatments.
UR - http://www.scopus.com/inward/record.url?scp=84861697039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861697039&partnerID=8YFLogxK
U2 - 10.1593/neo.12542
DO - 10.1593/neo.12542
M3 - Review article
C2 - 22745583
AN - SCOPUS:84861697039
VL - 14
SP - 368
EP - 375
JO - Neoplasia
JF - Neoplasia
SN - 1522-8002
IS - 5
ER -