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

Clara Meana, Ginesa García-Rostán, Lucía Peña, Gema Lordén, África Cubero, Antonio Orduña, B. Györffy, Jesús Balsinde, María A. Balboa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalJCI insight
Volume3
Issue number18
DOIs
Publication statusPublished - Sep 20 2018

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Phosphatidate Phosphatase
Colon
Carcinogenesis
Inflammation
Colonic Neoplasms
Colitis
Macrophages
Dextran Sulfate
Azoxymethane
Interleukin-23
lipine
Ulcerative Colitis
Neoplasms
Stem Cells
Cell Proliferation
Databases
Cytokines
Carcinoma

Keywords

  • Colorectal cancer
  • Gastroenterology
  • Inflammation
  • Inflammatory bowel disease
  • Macrophages

Cite this

Meana, C., García-Rostán, G., Peña, L., Lordén, G., Cubero, Á., Orduña, A., ... Balboa, M. A. (2018). The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis. JCI insight, 3(18). https://doi.org/10.1172/jci.insight.97506

The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis. / Meana, Clara; García-Rostán, Ginesa; Peña, Lucía; Lordén, Gema; Cubero, África; Orduña, Antonio; Györffy, B.; Balsinde, Jesús; Balboa, María A.

In: JCI insight, Vol. 3, No. 18, 20.09.2018.

Research output: Contribution to journalArticle

Meana, C, García-Rostán, G, Peña, L, Lordén, G, Cubero, Á, Orduña, A, Györffy, B, Balsinde, J & Balboa, MA 2018, 'The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis', JCI insight, vol. 3, no. 18. https://doi.org/10.1172/jci.insight.97506
Meana C, García-Rostán G, Peña L, Lordén G, Cubero Á, Orduña A et al. The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis. JCI insight. 2018 Sep 20;3(18). https://doi.org/10.1172/jci.insight.97506
Meana, Clara ; García-Rostán, Ginesa ; Peña, Lucía ; Lordén, Gema ; Cubero, África ; Orduña, Antonio ; Györffy, B. ; Balsinde, Jesús ; Balboa, María A. / The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis. In: JCI insight. 2018 ; Vol. 3, No. 18.
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