Sequencing of the human genome and transcriptome has left us with a monumental task of characterizing individual human genes using functional-genomics approaches. In the previous cycle of MBRS-SCORE program, we identified and preliminarily characterized a novel gene MGC10471/CCDC130, now referred as CCDC130 (NCBI nomenclature), from pancreatic cancer Expressed Sequence Tags (EST) libraries. In pilot studies, we have demonstrated that CCDC130 is (a) a mitochondrial protein (b) induced by Insulin-like growth factor (IGF-1)/insulin signaling (c) a putative target for Glycogen Synthase Kinase (GSK-3), Casein kinase 1 (CK1) and Casein kinase 2 (CK2) (d) down regulated in colon cancer and (e) siRNA mediated inhibition of CCDC130 protects COLO-357 pancreatic cancer cells from TRAIL induced apoptosis. Based on preliminary findings we propose following three specific aims. SA1: To investigate the role of CCDC130 in human colon cancer development by studying the expression of CCDC130 protein in colon cancer samples representing various stages of the disease. SA2: To study the role of CCDC130 in IGF-1/insulin signaling and determine whether CCDC130 is a target of GSK32, CK1 and CK2 kinases. SA3: Using genetic and pharmacologic modulators, we will study the in vitro effects of CCDC130 signaling on cancer cell proliferation, invasion, adhesion and migration. The continued funding of this proposal will ensure transition of the PI to non-SCORE RO1 like funding and increased participation of a minority serving institution like UDC in biomedical research.
The proposal aims to characterize a novel gene CCDC130 in cancer cell signaling. The proposal may lead to development of a novel cancer biomarker and/or a drug target. The proposal will catalyze PIs transition to non-SCORE funding mechanism and enhance biomedical research at a minority serving institution like UDC.
