{"entity": "publication", "iuid": "32637b3ae307431ea4b4bd2692d1c47b", "timestamp": "2026-08-29T04:23:47.927Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/32637b3ae307431ea4b4bd2692d1c47b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/32637b3ae307431ea4b4bd2692d1c47b"}}, "title": "LXR\u03b1 limits TGF\u03b2-dependent hepatocellular carcinoma associated fibroblast differentiation.", "authors": [{"family": "Mor\u00e9n", "given": "Anita", "initials": "A"}, {"family": "Bellomo", "given": "Claudia", "initials": "C"}, {"family": "Tsubakihara", "given": "Yutaro", "initials": "Y"}, {"family": "Kardassis", "given": "Dimitris", "initials": "D"}, {"family": "Mikulits", "given": "Wolfgang", "initials": "W"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH"}, {"family": "Moustakas", "given": "Aristidis", "initials": "A", "orcid": "0000-0001-9131-3827", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f11771bffabf4da6a2a5e2668c7c7c2d.json"}}], "type": "journal article", "published": "2019-05-16", "journal": {"title": "Oncogenesis", "issn": "2157-9024", "volume": "8", "issue": "6", "pages": "36", "issn-l": "2157-9024"}, "abstract": "Transforming growth factor \u03b2 (TGF\u03b2) is deposited in the extracellular space of diverse tissues. Resident fibroblasts respond to TGF\u03b2 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\u03b2 signaling. We report that agonist-activated liver X receptors (LXR) limit the expression of key components of myofibroblast differentiation, including the \u03b1-smooth muscle actin (\u03b1SMA) gene in liver cancer cells. CAFs derived from hepatocellular carcinoma (HCC) express high \u03b1SMA and low LXR\u03b1 levels, whereas hepatocarcinoma cells exhibit an inverse expression pattern. All hepatoma cells analyzed responded to the LXR\u03b1 agonist T0901317 by inducing fatty acid synthase (FASN) expression. On the other hand, T0901317 antagonized TGF\u03b2-induced fibroblastic marker responses, such as fibronectin and calponin, in a subset of hepatoma cells and all CAFs analyzed. Mechanistically, LXR\u03b1 antagonized TGF\u03b2 signaling at the transcriptional level. Smad3 and LXR\u03b1 were recruited to adjacent DNA motifs of the ACTA2 promoter. Upon cloning the human ACTA2 promoter, we confirmed its transcriptional induction by TGF\u03b2 stimulation, and LXR\u03b1 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\u03b1 agonists limit TGF\u03b2-dependent CAF differentiation, potentially limiting primary HCC growth.", "doi": "10.1038/s41389-019-0140-4", "pmid": "31097694", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6522550"}, {"db": "pii", "key": "10.1038/s41389-019-0140-4"}], "notes": [], "created": "2026-08-20T08:48:35.356Z", "modified": "2026-08-20T08:48:35.421Z"}