title: Vitamin D and Myofibroblasts in Fibrosis and Cancer: At Cross-purposes with TGF-β/SMAD Signaling.
abstract: The multifaceted involvement of the active vitamin D metabolite 1,25-dihydroxyvitamin D3(henceforth referred to by the synonyms 1,25(OH)2D3, calcitriol or vitamin D) in blunting the growth of cancer cells is amply recognized. In this review we focused our attention on the cross-talk between 1,25 (OH)2D3and the tumor microenvironment (TME), signaling out stromal cancer-associated fibroblasts (CAFs), the most abundant TME population, as a target for calcitriol anticancer action. In view of the commonality of the phenotypic signature in myofibroblasts, resident in the cancer stroma and in non-neoplastic fibrotic loci, we examined modes of action of vitamin D in non-neoplastic chronic diseases and in cancer to assess mechanistic similarities and divergences. A constant observation was that 1,25(OH)2D3or synthetic ligands via the active vitamin D receptor (VDR) impede transforming growth factor (TGF)-β/mothers against decapentaplegic homologs (SMADs) signaling in myofibroblasts regardless of the initiating insult. The translational impact of 1,25(OH)2D3in targetting stromal CAFs is discussed.
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheva, Israel.
authors.forename: Shraga
authors.initials: S
authors.lastname: Shany
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheva, Israel.|Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beersheva, Israel.
authors.forename: Ina
authors.initials: I
authors.lastname: Sigal-Batikoff
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheva, Israel sergiol@bgu.ac.il.|Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beersheva, Israel.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lamprecht
mesh_terms: D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D058628:Myofibroblasts / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C118756:dihydroxy-vitamin D3; D014807:Vitamin D
keywords: TGF-β/SMAD signaling; Vitamin D; cancer associated fibroblast; fibrosis; myofibroblast; review