Cancers 2014, 6(3), 1408-1440; doi:10.3390/cancers6031408
STAT3 in Cancer—Friend or Foe?
1
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 1Z2, Canada
2
The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China
*
Author to whom correspondence should be addressed.
Received: 17 April 2014 / Revised: 19 June 2014 / Accepted: 20 June 2014 / Published: 3 July 2014
(This article belongs to the Special Issue STAT3 Signalling in Cancer: Friend or Foe)
Abstract
The roles and significance of STAT3 in cancer biology have been extensively studied for more than a decade. Mounting evidence has shown that constitutive activation of STAT3 is a frequent biochemical aberrancy in cancer cells, and this abnormality directly contributes to tumorigenesis and shapes many malignant phenotypes in cancer cells. Nevertheless, results from more recent experimental and clinicopathologic studies have suggested that STAT3 also can exert tumor suppressor effects under specific conditions. Importantly, some of these studies have demonstrated that STAT3 can function either as an oncoprotein or a tumor suppressor in the same cell type, depending on the specific genetic background or presence/absence of specific coexisting biochemical defects. Thus, in the context of cancer biology, STAT3 can be a friend or foe. In the first half of this review, we will highlight the “evil” features of STAT3 by summarizing its oncogenic functions and mechanisms. The differences between the canonical and non-canonical pathway will be highlighted. In the second half, we will summarize the evidence supporting that STAT3 can function as a tumor suppressor. To explain how STAT3 may mediate its tumor suppressor effects, we will discuss several possible mechanisms, one of which is linked to the role of STAT3β, one of the two STAT3 splicing isoforms. Taken together, it is clear that the roles of STAT3 in cancer are multi-faceted and far more complicated than one appreciated previously. The new knowledge has provided us with new approaches and strategies when we evaluate STAT3 as a prognostic biomarker or therapeutic target.Keywords:
STAT3; oncoprotein; tumor suppressor; STAT3β; prognostic marker; therapeutic target
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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MDPI and ACS Style
Zhang, H.-F.; Lai, R. STAT3 in Cancer—Friend or Foe? Cancers 2014, 6, 1408-1440.