WNT/β-catenin signaling regulates mitochondrial activity to alter the oncogenic potential of melanoma in a PTEN-dependent manner

Brown, K, Yang, P, Salvador, D, Kulikauskas, R, Ruohola-Baker, H, Robitaille, A M, Chien, A J, Moon, R T and Sherwood, V (2017) WNT/β-catenin signaling regulates mitochondrial activity to alter the oncogenic potential of melanoma in a PTEN-dependent manner. Oncogene, 36. 3119–3136. ISSN 0950-9232

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    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.

    Item Type: Article
    Faculty \ School: Faculty of Science > School of Pharmacy
    University of East Anglia > Faculty of Science > Research Groups > Pharmaceutical Cell Biology
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    Depositing User: Pure Connector
    Date Deposited: 02 Feb 2017 03:50
    Last Modified: 25 Jul 2018 13:14
    URI: https://ueaeprints.uea.ac.uk/id/eprint/62282
    DOI: 10.1038/onc.2016.450

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