Targeting Wnt/β-catenin Signaling in Liver Cancers

As one of the critical contributing factors to hepatocellular carcinoma (HCC) growth, aberrant activation of Wnt/β-catenin signaling derives from a variety of molecular alterations involved in this pathway, especially mutations of β-catenin and AXIN1. Although a variety of drugs targeting Wnt/β-catenin signaling have been developed, most of them have not been thoroughly tested for liver cancer. In the current thesis, I first explored the effectiveness of two classes of drugs in a panel of HCC cell lines, i.e. an extracellular Wnt secretion inhibitor and cytosolic tankyrase inhibitor. Next, we compared the response and sensitivity for these inhibitors depending on the specific β-catenin signaling defect present in these HCC cell lines, i.e. CTNNB1 or AXIN1 mutations and achieved a better understanding of the mechanism through which AXIN1 mutations contribute to HCC cell growth. Lastly, we found STRAP as a new potential molecular target regulating Wnt/β-catenin signaling in HCC.

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