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Journal article
Regulation of lipid synthesis by the RNA helicase Mov10 controls Wnt5a production
Oncogenesis (New York, NY), v 4(6), pp e154-e154
01 Jun 2015
PMID: 26029828
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Regulation of lipid synthesis by the RNA helicase Mov10 controls Wnt5a production
- Creators
- W. Wang - University of PennsylvaniaN. Snyder - Drexel UniversityA. J. Worth - University of PennsylvaniaI. A. Blair - University of PennsylvaniaE. S. Witze - University of Pennsylvania
- Publication Details
- Oncogenesis (New York, NY), v 4(6), pp e154-e154
- Publisher
- Springer Nature
- Number of pages
- 11
- Grant note
- T32GM008076 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) CA181633 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01CA181633 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Melanoma Research Foundation IRG-78-002-35 / American Cancer Society T32ES019851 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000358718900005
- Scopus ID
- 2-s2.0-84931273474
- Other Identifier
- 991019167850504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology