Sam68 regulates colon tumorigenesis by genotoxic stress-induced NF-kB activation

JOINT EVENT:25^th World Congress on CANCER SCIENCE AND THERAPY & 10^th World Congress on BIOMARKERS & CLINICAL RESEARCH

October 18-20, 2017 Baltimore, USA

Kai Fu

Johns Hopkins University, USA

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

Nuclear factor kappa B (NF-���������������ºB) is a transcription factor that controls genes for cell survival and NF-���������������ºB signaling has emerged as one of the most important mediators of the cellular response to genotoxic stresses. Genotoxic agents trigger a �������¢����������������nuclearto-cytoplasmic�������¢���������������� NF-���������������ºB activation signaling pathway; however, the early events controlling the initiation of the signaling pathway is poorly understood. Our data demonstrate that Src-associated-substrate-during-mitosis-of-68 kDa/KH domain containing, RNA binding, signal transduction associated 1 (Sam68/ KHDRBS1) plays a key role in genotoxic stress-initiated NF-���������������ºB signaling pathway. Sam68 directly binds to Poly (ADP-ribose) polymerase 1 (PARP1) and regulates PARP1 enzymatic activity in vitro. Sam68 deficiency abolishes DNA damage-stimulated polymers of ADP-ribose (PAR) production and the PAR-dependent NF-���������������ºB transactivation of antiapoptotic genes. Sam68 null cells are hypersensitive to genotoxicity caused by genotoxic agents. Up-regulated Sam68 coincides with elevated PAR production and NF-���������������ºB activation in human and mouse colon cancer. Interference with Sam68 protein sensitizes human colon cancer cells to genotoxic stress-induced apoptosis and the hypersensitivity is abolished by ectopic expression of constitutively activated NF-���������������ºB. Further, genetic deletion of Sam68 substantially alleviates colon tumor burden in mice model. Taken together, our findings reveal a novel function of Sam68 in the genotoxic stress-initiated nuclear signaling, which is critical for colon tumorigenesis.

Biography :

Kai Fu has completed his PhD from the University of Science and Technology of China. He started his Post-doctoral training in the Department of Biochemistry and Molecular Biology at Johns Hopkins Bloomberg School of Public Health since 2012.