The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis

• DOI: 10.1172/jci.insight.97506
• Publication Date: 2018-09-19T15:01:59Z
• Authors: Clara Meana; Ginesa García-Rostán; Lucía Peña; Gema Lordén; África Cubero; Antonio Orduña; Balázs Győrffy; Jesús Balsinde; María A. Balboa
• Keywords: 0301 basic medicine; Carcinogenesis; Colon; Chemokine CXCL1; Chemokine CXCL2; Azoxymethane; 610; Interleukin-23; Mice; 03 medical and health sciences; Animals; Humans; Cell Proliferation; Inflammation; Mice, Inbred BALB C; tumorok; Macrophages; Dextran Sulfate; onkológia; Colitis; Inflammatory Bowel Diseases; 3. Good health; Disease Models, Animal; Colonic Neoplasms; Cytokines; Female; RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok

Colon cancer is a devastating illness that associated with gut inflammation. Here, we explored the possible role of lipin-1, phosphatidic acid phosphatase, in development colitis-associated tumorigenesis. Azoxymethane and dextran sodium sulfate-treated (DSS-treated) animals deficient lipin-1 harbored fewer tumors carcinomas than WT due to decreased cellular proliferation, lower expression antiapoptotic protumorigenic factors, reduced infiltration macrophages colon tumors. They also displayed increased resistance DSS-induced colitis by producing less proinflammatory cytokines experiencing immune infiltration. Lipin-1-deficient from were activated phosphatase activity isolated DSS-treated animals. Transference into lipin-1-deficient was sufficient increase burden. Furthermore, treatment mice IL-23 exacerbated Analysis human databases ulcerative patients showed those disorders correlates markers CXCL1 CXCL2. And finally, clinically, LPIN1 had prognostic value inflammatory stem-cell subtypes cancers. Collectively, these data demonstrate critical regulator intestinal inflammation inflammation-driven development.