Poster #046
The Role of CD44-ICD in Liver Cancer Initiation and Chemoresistance
Mentors: Barun Das, PhD; PI: Debanjan Dhar, PhD
The origin of cancer stem cells (CSCs) in liver cancer remains unclear. CD44, a known CSC marker linked to poor prognosis in hepatocellular carcinoma (HCC), has an intracellular domain (ICD) capable of nuclear translocation. This nuclear CD44-ICD is observed in most human HCC tumors, though its function is not well understood. We hypothesize that CD44-ICD contributes to liver cancer initiation by transforming differentiated hepatocytes and generating an initial CSC pool. It may enhance proliferation and inhibit P53-mediated cell death, promoting resistance to oncogenic stress and chemotherapy. To test this, we re-expressed HA-tagged CD44-ICD in CD44 knockout (KO) liver cancer cells and compared their growth, survival, and cisplatin response to KO controls. We also assessed its impact on tumor initiation in mice. Preliminary findings suggest CD44-ICD increases proliferation and chemoresistance, pointing to a potential role in liver cancer progression. Further studies are needed to clarify its mechanisms.