One of the most aggressive and common forms of liver cancer is hepatocellular carcinoma. A team of researchers from the Institute of Cancer Research at the Medical University of Vienna (MedUni Vienna) has now identified the crucial factor involved in the development and progression of this malignant type of tumor: namely, the AXL receptor, which supports cancer-promoting processes and slows down cancer-inhibiting factors. This key finding could make a targeted therapeutic approach possible in future. In the Western world, metabolic diseases and infections with hepatitis C are the most common causes of hepatocellular carcinoma (HCC). The team led by Dr. Wolfgang Mikulits, Head of the Tumor Progression and Metastasis Research Group at the MedUni Vienna Institute of Cancer Research (ICR) and member of the Comprehensive Cancer Center (CCC) Vienna, investigated the role of the AXL receptor tyrosine kinase in the context of liver cancer as part of a study. Says Dr. Mikulits: "Until now, the function of AXL had been barely investigated at all, which is astonishing since this receptor is shown to have been activated in more than 50 per cent of all HCC patients." The researchers were able to demonstrate that the expression and activation of AXL lead to a diversion of signaling pathways, enabling the migration and metastasis of liver cancer cells. As a result, AXL, after binding a 14-3-3 adapter protein, is able to influence the extremely important transforming growth factor beta (TGF-beta) signaling pathway in such a way that it only causes the invasion and metastasis of HCC cells. In contrast to this, AXL inhibits the anti-oncogenic function of TGF-beta. AXL is therefore the crucial factor in the aggressive development of hepatocellular carcinoma.
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