Li Ka Shing Faculty of Medicine, The University of Hong Kong
Hepatocellular carcinoma (HCC) is a primary malignancy of liver and develops preponderantly in individuals with underlying chronic liver disease. HCC is an aggressive tumor with local invasion and extrahepatic metastasis as signatures in the advanced stage. Patients with an advanced HCC stage are precluded from curative treatment and are limited to only palliative therapy. This stresses the urgent need to ascertain the underlying basis of cancer metastasis and the clinical importance to identify sensitive and specific biomarkers for early detection of HCC.
Yam Laboratory focuses on the study of liver cancer, particularly the process of metastasis. Using multidisciplinary approaches, we are endeavoring to understand the mechanistic basis of HCC metastasis with translational impact leading to improved health, well-being and quality of life for cancer patients.
Acquisition of migratory and invasive behaviors is fundamental to cancer cells to metastasize. We have particular interest in focal adhesion proteins which play pivotal role in the regulation of cell motility. Focal adhesion proteins form structural links between extracellular matrix and actin cytoskeleton, and are important sites of signal transduction. Dysregulation of focal adhesion proteins has been implicated in various cancers and contributed to the acquired metastatic behavior of cancer cells. We have a long-standing interest in the study of DLC (deleted in liver cancer) family of tumor suppressors and caveolin-1. These molecules are closely associated with liver cancer, and their deregulation contributes to the acquired aggressiveness of cancer cells. Our work has answered fundamental questions about the subcellular localization, intracellular translocation and binding activity of these molecules as well as having unveiled their molecular regulation by phosphorylation that underlies liver cancer progression.
Metastasis to specific organs is not a random process but results from the interplay between intrinsic properties of cancer cells and microenvironment of the distant organ. Extracellular vesicle (EV) shedding from tumor cells has emerged as an important channel for cell-cell communication in influencing the local tumor microenvironment and facilitating pre-metastatic niche formation in distant organ sites. They contain distinct components which depend on the cell type from which they are released and can subsequently be transferred to the recipient cells. EV content is regarded as a fingerprint of the releasing cells; it provides insightful information about the origin and functions of releasing cells. Circulating EV of cancer patients may therefore serve as promising biomarker for early detection and prognosis. We are interested to understand the molecular basis of EV-driven HCC metastasis by dissecting the functional role and signaling cascades of exosomal content. In clinical perspective, our work aims to identify promising exosomal content for the early diagnosis and novel therapeutic interventions for cancer patients.