Yousef Salama
An-Najah National University, Palestine
Title: Fibrinolytic factors promote inflammatory colonic carcinogenesis through miR- 126-mediated targeting of the proteolytic niche
Biography
Biography: Yousef Salama
Abstract
Inflammation is a well-established driver of carcinogenesis and inflammatory bowel disease patients have an increased risk of developing Colorectal Cancer (CRC). We found high intratumoral expression of the fibrinolytic factor Tissue-type Plasminogen Activator (tPA) in human colorectal tissues. Using the azoxymethane/dextran sodium sulfate-induced inflammation-associated colon carcinogenesis model, we demonstrate that tPA and plasmin are up-regulated during colon carcinogenesis. Genetic and pharmacological inhibition of plasmin or tPA suppressed inflammation-induced tumor formation in AOM/DSS induced mice. Mechanistically, tPA downregulated AP2a and miR-126 by activating NF-kB signaling. Furthermore, tPA via miR126 deregulates factors like HB-EGF, proteases (tPA or MMP9) and CCL2 that are known to promote inflammation-induced CRC. Taken together, our study indicates that targeting plasmin may be useful in the prevention of colon cancer in individuals with inflammatory bowel disease.