Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the third leading cause of cancer-related deaths worldwide. Hepatocyte growth factor (HGF)/c-Met signaling is particularly important in the development of HCC as it controls growth, survival, migration and differentiation of tumor cells. Others and we have shown that abnormalities in HGF/c-Met signaling are implicated in tumor development and progression in a variety of cancers. The increase in c-Met expressing stem/progenitor cells in the liver is required for hepatocarcinogenesis, and high c-Met expression is correlated with metastasis, poor prognosis, and drug resistance. An elevated HGF level is uncommon in tumorigenesis except for breast tumors. Therefore, ligand-independent c-Met activation in HCC is a critical phenomenon that should be investigated further.RESEARCH INTERESTS
Our group is focused on signaling pathways that modulate the growth, motility, and invasion of hepatocellular carcinoma and using this molecular knowledge to improve the diagnosis and treatment of HCC. Our aim is to understand the molecular mechanisms behind the aggressive behavior and drug resistance in HCC and to translate this molecular knowledge to improve diagnosis and treatment.
Currently, our projects encompass:
1) The molecular mechanisms of HGF/c-Met mediated invasion and metastasis in HCC, 2) The effects of tumor microenvironment on the regulation of signaling networks and cellular behaviors of HCC, 3) The roles of non-coding RNAs in the regulation of c-Met signaling in HCC, 4) Fabrication and validation of a new lab-on-a-chip device for early diagnosis of metastasis.
In the next 5 years, we aim to:
• Identify the role of HGF/c-Met signaling in the regulation of glucose metabolism in HCC and further use this knowledge for developing strategies to prevent HCC. • Understand the functional role of the HGF/c-Met axis in acquired sorafenib resistance in HCC cells and to improve targeted therapies of HCC patients. • Fabricate and validate a Lab-on-a-chip (LOC) system that can predict the metastatic and invasive ability to circulate tumor cells (CTCs) in HCC and that can also determine the effects of drugs on tumor metastasis.