dc.contributor.author |
Meana Clara |
|
dc.contributor.author |
García-Rostán Ginesa |
|
dc.contributor.author |
Peña Lucía |
|
dc.contributor.author |
Lordén Gema |
|
dc.contributor.author |
Cubero África |
|
dc.contributor.author |
Orduña Antonio |
|
dc.contributor.author |
Győrffy, Balázs |
|
dc.contributor.author |
Balsinde Jesús |
|
dc.contributor.author |
Balboa María A |
|
dc.date.accessioned |
2019-06-24T06:42:14Z |
|
dc.date.available |
2019-06-24T06:42:14Z |
|
dc.date.issued |
2018 |
|
dc.identifier.citation |
journalVolume=3;journalIssueNumber=18;pagination=97506, pages: 16;journalTitle=JCI INSIGHT;journalAbbreviatedTitle=JCI INSIGHT; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/6830 |
|
dc.identifier.uri |
doi:10.1172/jci.insight.97506 |
|
dc.description.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. |
|
dc.relation.ispartof |
urn:issn:2379-3708 |
|
dc.title |
The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis |
|
dc.type |
Journal Article |
|
dc.date.updated |
2019-03-05T12:10:26Z |
|
dc.language.rfc3066 |
en |
|
dc.rights.holder |
NULL |
|
dc.identifier.mtmt |
30309634 |
|
dc.identifier.wos |
000445115700003 |
|
dc.identifier.pubmed |
30232275 |
|
dc.contributor.department |
SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika |
|
dc.contributor.institution |
Semmelweis Egyetem |
|