Search: onr:"swepub:oai:DiVA.org:uu-387277" >
LXR alpha limits TG...
LXR alpha limits TGF beta-dependent hepatocellular carcinoma associated fibroblast differentiation
-
- Morén, Anita (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Ludwiginstitutet för cancerforskning
-
- Bellomo, Claudia (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Ludwiginstitutet för cancerforskning
-
- Tsubakihara, Yutaro (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Ludwiginstitutet för cancerforskning
-
show more...
-
- Kardassis, Dimitris (author)
- Univ Crete, Med Sch, Dept Biochem, Iraklion 71003, Crete, Greece
-
- Mikulits, Wolfgang (author)
- Med Univ Vienna, Comprehens Canc Ctr Vienna, Div Inst Canc Res, Dept Med 1, Vienna, Austria
-
- Heldin, Carl-Henrik, 1952- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
-
- Moustakas, Aristidis (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Ludwiginstitutet för cancerforskning
-
show less...
-
(creator_code:org_t)
- 2019-05-16
- 2019
- English.
-
In: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 8
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://uu.diva-port... (primary) (Raw object)
-
https://www.nature.c...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Transforming growth factor beta (TGF beta) is deposited in the extracellular space of diverse tissues. Resident fibroblasts respond to TGF beta and undergo myofibroblastic differentiation during tissue wound healing and cancer progression. Cancer-associated fibroblasts (CAFs) communicate with tumor cells during cancer progression, under the guidance of TGF beta signaling. We report that agonist-activated liver X receptors (LXR) limit the expression of key components of myofibroblast differentiation, including the a-smooth muscle actin (alpha SMA) gene in liver cancer cells. CAFs derived from hepatocellular carcinoma (HCC) express high aSMA and low LXR alpha levels, whereas hepatocarcinoma cells exhibit an inverse expression pattern. All hepatoma cells analyzed responded to the LXR alpha agonist T0901317 by inducing fatty acid synthase (FASN) expression. On the other hand, T0901317 antagonized TGF beta-induced fibroblastic marker responses, such as fibronectin and calponin, in a subset of hepatoma cells and all CAFs analyzed. Mechanistically, LXR alpha antagonized TGF beta signaling at the transcriptional level. Smad3 and LXR alpha were recruited to adjacent DNA motifs of the ACTA2 promoter. Upon cloning the human ACTA2 promoter, we confirmed its transcriptional induction by TGF beta stimulation, and LXR alpha overexpression repressed the promoter activity. Hepatosphere formation by HCC cells was enhanced upon co-culturing with CAFs. T0901317 suppressed the positive effects exerted on hepatosphere growth by CAFs. Taken together, the data suggest that LXR alpha agonists limit TGF beta-dependent CAF differentiation, potentially limiting primary HCC growth.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database