Contextual Regulation of TGF-β Signaling in Liver Cancer.
Primary liver cancer is one of the leading causes for cancer-related death worldwide. Transforming growth factor beta (TGF-β) is a pleiotropic cytokine that signals through membrane receptors and intracellular Smad proteins, which enter the nucleus upon receptor activation and act as transcription factors. TGF-β inhibits liver tumorigenesis in the early stage by inducing cytostasis and apoptosis, but promotes malignant progression in more advanced stages by enhancing cancer cell survival, EMT, migration, invasion and finally metastasis. Understanding the molecular mechanisms underpinning the multi-faceted roles of TGF-β in liver cancer has become a persistent pursuit during the last two decades. Contextual regulation fine-tunes the robustness, duration and plasticity of TGF-β signaling, yielding versatile albeit specific responses. This involves multiple feedback and feed-forward regulatory loops and also the interplay between Smad signaling and non-Smad pathways. This review summarizes the known regulatory mechanisms of TGF-β signaling in liver cancer, and how they channel, skew and even switch the actions of TGF-β during cancer progression.
['Tu|Shuo|S|', 'Huang|Wei|W|', 'Huang|Chunhong|C|', 'Luo|Zhijun|Z|', 'Yan|Xiaohua|X|']
D006528:Carcinoma, Hepatocellular D018450:Disease Progression D058750:Epithelial-Mesenchymal Transition D025461:Feedback, Physiological D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008113:Liver Neoplasms D009361:Neoplasm Invasiveness D015398:Signal Transduction D051785:Smad Proteins D016212:Transforming Growth Factor beta
contextual regulation TGF-β signaling liver cancer Smad cytostasis hepatocellular carcinoma