title: Regulation of lipid synthesis by the RNA helicase Mov10 controls Wnt5a production.
abstract: Expression of the Wnt ligand Wnt5a is frequently elevated in melanoma and is thought to be a critical regulator of cell movement during metastasis. However, the mechanisms regulating its expression are unknown. We find that the level of secreted Wnt5a varies by as much as 10-fold between cell lines and correlates more strongly with invasion than total cellular levels. Our results indicate that the RNA helicase Mov10 plays a role in Wnt5a synthesis and secretion. Inhibition of Mov10 increases secreted Wnt5a levels in melanoma cells by increasing Wnt5a synthesis and acylation. This is achieved by increasing fatty acid synthase (FASN) and stearoyl-CoA desaturase expression, leading to elevated levels of palmitoleoyl-CoA, required for Wnt ligand lipid modification and secretion. Melanoma tumors exhibit reduced expression of Mov10 compared with benign nevi and Mov10 levels inversely correlate with FASN levels in primary tumors. These results reveal a previously unappreciated role for aberrant lipid metabolism in regulating Wnt5a signaling that may be a critical step in melanoma progression.
authors.affiliation: 1] Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA [3] Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Philadelphia, PA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1] Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Philadelphia, PA, USA [2] Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA [3] Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA [4] AJ Drexel Autism Institute, Drexel University, Philadelphia, PA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Snyder
authors.affiliation: 1] Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Philadelphia, PA, USA [2] Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA [3] Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Worth
authors.affiliation: 1] Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Philadelphia, PA, USA [2] Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA [3] Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Blair
authors.affiliation: 1] Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA [2] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA [3] Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Philadelphia, PA, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Witze