Transforming growth factor-β as a therapeutic target in hepatocellular carcinoma.
نویسندگان
چکیده
Hepatocellular carcinoma arises in patients as a consequence of long-standing preexisting liver illnesses, including viral hepatitis, alcohol abuse, or metabolic disease. In such preexisting liver diseases, TGF-β plays an important role in orchestrating a favorable microenvironment for tumor cell growth and promoting epithelial-mesenchymal transition (EMT). TGF-β signaling promotes hepatocellular carcinoma progression by two mechanisms: first, via an intrinsic activity as an autocrine or paracrine growth factor and, second, via an extrinsic activity by inducing microenvironment changes, including cancer-associated fibroblasts, T regulatory cells, and inflammatory mediators. Although there is an increasing understanding on how TGF-β signaling is associated with tumor progression in hepatocellular carcinoma, it is not clear whether TGF-β signaling is limited to a certain subgroup of patients with hepatocellular carcinoma or is a key driver of hepatocellular carcinoma during the entire tumorigenesis of hepatocellular carcinoma. Inhibitors of the TGF-β signaling have been shown to block hepatocellular carcinoma growth and progression by modulating EMT in different experimental models, leading to the clinical investigation of the TGF-β inhibitor LY2157299 monohydrate in hepatocellular carcinoma. Preliminary results from a phase II clinical trial have shown improved clinical outcome and also changes consistent with a reduction of EMT.
منابع مشابه
Nanocurcumin-Mediated Down-Regulation of Telomerase Via Stimulating TGFβ1 Signaling Pathway in Hepatocellular Carcinoma Cells
Background: Curcumin, extracted from turmeric, represents enormous potential to serve as an anticancer agent. Telomerase is viewed as a prominent molecular target of curcumin, and transforming growth factor-β1 (TGFβ1) has proven to be a major inhibitory signaling pathway for telomerase activity. In the current study, we aimed to explore suppressive effects of nanocurcumin on telomeras...
متن کاملTGF-β Mediated Crosstalk Between Malignant Hepatocyte and Tumor Microenvironment in Hepatocellular Carcinoma
In this article, we have reviewed current literature regarding the regulation of hepatocellular carcinoma (HCC) by the interaction of malignant hepatocytes and their tissue environment through cytokine signaling, here represented by transforming growth factor-beta (TGF-β) signaling. We have discussed responses of TGF-β signaling in transition of hepatic stellate cells to myofibroblasts (MFBs), ...
متن کاملTRANSFORMING GROWTH FACTOR β2 UP-REGULATES GM-CSF GENE IN HUMAN BLADDER CARCINOMA CELL LINE HTB 5637
Transforming growth factor betas are multifunctional polypeptides in the cytokine superfamily. They have a growth inhibitory role on hemopoietic progenitor cells in semisolid colony assay as well as in long-term bone-marrow culture. TGF - β2 represses stromal cells, stem cell factor gene transcription, and decreases the stability of c-kit transcripts in hemopoietic cells. TGF-β also modulat...
متن کاملAnti-hepatocellular carcinoma properties of the anti-alcoholism drug disulfiram discovered to enzymatically inhibit the AMPK-related kinase SNARK in vitro
We recently described that the anti-apoptotic AMPK-related kinase, SNARK, promotes transforming growth factor (TGF)-β signaling in hepatocellular carcinoma (HCC) cells, as a potentially new therapeutic target. Here we explored FDA-approved drugs inhibiting the enzymatic activity of SNARK, using an in vitro luminescence kinase assay system. Interestingly, the long-used anti-alcoholism drug disul...
متن کاملTGF-β Induces Degradation of PTHrP Through Ubiquitin-Proteasome System in Hepatocellular Carcinoma
Both transforming growth factor-β (TGF-β) and parathyroid hormone-related protein (PTHrP) regulate important cellular processes, such as apoptosis in the development of hepatocellular carcinoma. However, the mechanisms of regulation of PTHrP by TGF-β are largely unknown. We hypothesized that TGF-β regulates the expression of PTHrP protein through a post-translational mechanism. Using hepatocell...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Cancer research
دوره 74 7 شماره
صفحات -
تاریخ انتشار 2014