Hepatic stem cells and transforming growth factor β in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. It arises from modulation of multiple genes by mutations, epigenetic regulation, noncoding RNAs and translational modifications of encoded proteins. Although >40% of HCCs are clonal and thought to arise from cancer stem cells (CSCs), the precise identification and mechanisms of CSC formation remain poorly understood. A functional role of transforming growth factor (TGF)-β signalling in liver and intestinal stem cell niches has been demonstrated through mouse genetics. These studies demonstrate that loss of TGF-β signalling yields a phenotype similar to a human CSC disorder, Beckwith-Wiedemann syndrome. Insights into this powerful pathway will be vital for developing new therapeutics in cancer. Current clinical approaches are aimed at establishing novel cancer drugs that target activated pathways when the TGF-β tumour suppressor pathway is lost, and TGF-β itself could potentially be targeted in metastases. Studies delineating key functional pathways in HCC and CSC formation could be important in preventing this disease and could lead to simple treatment strategies; for example, use of vitamin D might be effective when the TGF-β pathway is lost or when wnt signalling is activated.
Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Avijit
A
Majumdar
Steven A
SA
Curley
Xifeng
X
Wu
Powel
P
Brown
Jessica P
JP
Hwang
Kirti
K
Shetty
Zhi-Xing
ZX
Yao
Aiwu Ruth
AR
He
Shulin
S
Li
Lior
L
Katz
Patrizia
P
Farci
Lopa
L
Mishra
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta