title: TGF-β signaling in liver and gastrointestinal cancers.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: L H
authors.initials: LH
authors.lastname: Katz
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Likhter
authors.affiliation: Institute for Clinical Research, Veterans Affairs Medical Center, Washington, DC, USA.
authors.forename: W
authors.initials: W
authors.lastname: Jogunoori
authors.affiliation: Institute for Clinical Research, Veterans Affairs Medical Center, Washington, DC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Belkin
authors.affiliation: Institute for Clinical Research, Veterans Affairs Medical Center, Washington, DC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ohshiro
authors.affiliation: Department of Surgery and GWU Cancer Center, George Washington University and DVAMC, Washington, DC, USA. Electronic address: lopamishra2@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Mishra
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta
keywords: Cancers; GI cancers; Liver cancer; TGF-β signaling