RT info:eu-repo/semantics/article
T1 The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis
A1 Meana González, Clara
A1 García-Rostán y Pérez, Ginesa María
A1 Peña, Lucía
A1 Lordén, Gema
A1 Cubero, África
A1 Orduña Domingo, Antonio
A1 Győrffy, Balázs
A1 Balsinde Rodríguez, Jesús
A1 Balboa García, María Ángeles
K1 Gastroenterología
K1 Inflamación
K1 Oncología
K1 Oncología
K1 Bioquímica
K1 Inmunología
K1 Patología
K1 2411 Fisiología Humana
K1 2302 Bioquímica
K1 2412 Inmunología
AB Colon cancer is a devastating illness that is associated with gut inflammation. Here, we explored the possible role of lipin-1, a phosphatidic acid phosphatase, in the development of colitis-associated tumorigenesis. Azoxymethane and dextran sodium sulfate-treated (DSS-treated) animals deficient in lipin-1 harbored fewer tumors and carcinomas than WT animals due to decreased cellular proliferation, lower expression of antiapoptotic and protumorigenic factors, and a reduced infiltration of macrophages in colon tumors. They also displayed increased resistance to DSS-induced colitis by producing less proinflammatory cytokines and experiencing less immune infiltration. Lipin-1-deficient macrophages from the colon were less activated and displayed lower phosphatidic acid phosphatase activity than WT macrophages isolated from DSS-treated animals. Transference of WT macrophages into lipin-1-deficient animals was sufficient to increase colitis burden. Furthermore, treatment of lipin-1-deficient mice with IL-23 exacerbated colon inflammation. Analysis of human databases from colon cancer and ulcerative colitis patients showed that lipin-1 expression is increased in those disorders and correlates with the expression of the proinflammatory markers CXCL1 and CXCL2. And finally, clinically, LPIN1 expression had prognostic value in inflammatory and stem-cell subtypes of colon cancers. Collectively, these data demonstrate that lipin-1 is a critical regulator of intestinal inflammation and inflammation-driven colon cancer development.
PB American Society for Clinical Investigation
YR 2018
FD 2018
LK https://uvadoc.uva.es/handle/10324/79494
UL https://uvadoc.uva.es/handle/10324/79494
LA eng
NO JCI Insight, Sep 2018, vol. 3, n. 18, p. e97506
NO Producción Científica
DS UVaDOC
RD 23-mar-2026