title: WNT/β-catenin signaling regulates mitochondrial activity to alter the oncogenic potential of melanoma in a PTEN-dependent manner.
abstract: Aberrant regulation of WNT/β-catenin signaling has a crucial role in the onset and progression of cancers, where the effects are not always predictable depending on tumor context. In melanoma, for example, models of the disease predict differing effects of the WNT/β-catenin pathway on metastatic progression. Understanding the processes that underpin the highly context-dependent nature of WNT/β-catenin signaling in tumors is essential to achieve maximal therapeutic benefit from WNT inhibitory compounds. In this study, we have found that expression of the tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alters the invasive potential of melanoma cells in response to WNT/β-catenin signaling, correlating with differing metabolic profiles. This alters the bioenergetic potential and mitochondrial activity of melanoma cells, triggered through regulation of pro-survival autophagy. Thus, WNT/β-catenin signaling is a regulator of catabolic processes in cancer cells, which varies depending on the metabolic requirements of tumors.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, UK.
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Yang
authors.affiliation: Division of Cancer Research, Jacqui Wood Cancer Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: D
authors.initials: D
authors.lastname: Salvador
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kulikauskas
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ruohola-Baker
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Robitaille
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA.|Division of Dermatology, University of Washington, Seattle, WA, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Chien
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Moon
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, UK.|Division of Cancer Research, Jacqui Wood Cancer Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: V
authors.initials: V
authors.lastname: Sherwood
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008928:Mitochondria / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse