TY - JOUR
T1 - TGF-β signaling in liver and gastrointestinal cancers
AU - Katz, L. H.
AU - Likhter, M.
AU - Jogunoori, W.
AU - Belkin, M.
AU - Ohshiro, K.
AU - Mishra, L.
N1 - Publisher Copyright:
© 2016 Elsevier Ireland Ltd
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Transforming Growth Factor-β (TGF-β) plays crucial and complex roles in liver and gastrointestinal cancers. These include a multitude of distinct functions, such as maintaining stem cell homeostasis, promoting fibrosis, immune modulating, as a tumor suppressor and paradoxically, as a tumor progressor. However, key mechanisms for the switches responsible for these distinct actions are poorly understood, and remain a challenge. The Cancer Genome Atlas (TCGA) analyses and genetically engineered mouse models now provide an integrated approach to dissect these multifaceted and context-dependent driving roles of the TGF-β pathway. In this review, we will discuss the molecular mechanisms of TGF-β signaling, focusing on colorectal, gastric, pancreatic, and liver cancers. Novel drugs targeting the TGF-β pathway have been developed over the last decade, and some have been proven effective in clinical trials. A better understanding of the TGF-β pathway may improve our ability to target it, thus providing more tools to the armamentarium against these deadly cancers.
AB - Transforming Growth Factor-β (TGF-β) plays crucial and complex roles in liver and gastrointestinal cancers. These include a multitude of distinct functions, such as maintaining stem cell homeostasis, promoting fibrosis, immune modulating, as a tumor suppressor and paradoxically, as a tumor progressor. However, key mechanisms for the switches responsible for these distinct actions are poorly understood, and remain a challenge. The Cancer Genome Atlas (TCGA) analyses and genetically engineered mouse models now provide an integrated approach to dissect these multifaceted and context-dependent driving roles of the TGF-β pathway. In this review, we will discuss the molecular mechanisms of TGF-β signaling, focusing on colorectal, gastric, pancreatic, and liver cancers. Novel drugs targeting the TGF-β pathway have been developed over the last decade, and some have been proven effective in clinical trials. A better understanding of the TGF-β pathway may improve our ability to target it, thus providing more tools to the armamentarium against these deadly cancers.
KW - Cancers
KW - GI cancers
KW - Liver cancer
KW - TGF-β signaling
UR - http://www.scopus.com/inward/record.url?scp=84962911049&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2016.03.033
DO - 10.1016/j.canlet.2016.03.033
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C2 - 27039259
AN - SCOPUS:84962911049
SN - 0304-3835
VL - 379
SP - 166
EP - 172
JO - Cancer Letters
JF - Cancer Letters
IS - 2
ER -