The role of FADD in pancreatic cancer cell proliferation and drug resistance.

Abstract

Pancreatic cancer has one of the poorest patient outcomes and is highly resistant to chemotherapy. Identifying the molecular mechanisms involved in drug resistance is critical in the development of novel strategies to treat pancreatic cancer. The results of the present study demonstrate that Fas-associated death domain protein (FADD), a classical adaptor protein mediating apoptotic stimuli-induced cell death, protects pancreatic cancer cells from drug-induced apoptosis. In contrast to its classical apoptotic roles, it was observed that FADD is required for pancreatic cancer cell proliferation and that it is overexpressed to varying degrees in various types of pancreatic cancer cell. This leads to differing levels of drug resistance in pancreatic cancer cells, where drug resistance is positively correlated with FADD expression. Notably, the results of the present study demonstrate that FADD protects pancreatic cancer cells from drug-induced apoptosis, while RNA interference of FADD sensitizes drug-resistant cells to Adriamycin®-mediated apoptosis. The results of the present study reveal unexpected roles for FADD in pancreatic cancer cell proliferation and drug resistance.