Multiple signal pathways in obesity-associated cancer

Chen, J. (2011) Multiple signal pathways in obesity-associated cancer. Obesity Reviews, 12 12: 1063-1070. doi:10.1111/j.1467-789X.2011.00917.x


Author Chen, J.
Title Multiple signal pathways in obesity-associated cancer
Journal name Obesity Reviews   Check publisher's open access policy
ISSN 1467-789X
1467-7881
Publication date 2011-12-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1111/j.1467-789X.2011.00917.x
Volume 12
Issue 12
Start page 1063
End page 1070
Total pages 8
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell
Language eng
Abstract Obesity is increasing worldwide and reaches to a large proportion of the population in developed countries. Thus, obesity-associated cancer has become a major health problem. Multiple cancer risk factors in obesity have been identified including insulin/insulin-like growth factor axis, adipokines and cytokines; and multiple intracellular signal pathways have been studied. However, the role of each signal pathway in obesity-associated cancer is controversial. In this review, the recent studies on signal pathways in obesity-associated cancer are summarized and a unified explanation is provided. Multiple risk factors could initially activate phosphoinositide 3-kinase (PI3K/Akt), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) pathways. With increased severity of obesity, mammalian target of rapamycin (mTOR), which is down-stream of both PI3K/Akt and MAPK, is highly activated. Activated mTOR in turn inhibits the PI3K/Akt pathway and further activates the STAT3 pathway. This may explain the activation of the PI3K/Akt pathway at the early stage of obesity and its inhibition at the later stage. mTOR inhibition may be used for cancer therapy, but it may be necessary to be combined with the PI3K/Akt inhibitor as decreased mTOR activity will release its feedback inhibition on the PI3K/Akt pathway, which is under the influence of multiple cancer risk factors in obesity. Thus, dual inhibitors of PI3K and mTOR may provide a novel approach.
Keyword MAPK
Obesity-associated cancer
PI3K/Akt/mTOR
STAT3
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Biomedical Sciences Publications
 
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Created: Fri, 14 Mar 2014, 00:01:42 EST by Jiezhong Chen on behalf of School of Biomedical Sciences