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

Kate Brown; Peggy Yang; Daniela Nobre Salvador; Rima Kulikauskas; Hannele Ruohola-Baker; Aaron M. Robitaille; Andy J. Chien; Randall T. Moon; Victoria Sherwood

doi:10.1038/onc.2016.450

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

Kate Brown
, Peggy Yang
, Daniela Nobre Salvador
, Rima Kulikauskas
, Hannele Ruohola-Baker
, Aaron M. Robitaille
, Andy J. Chien
, Randall T. Moon
, Victoria Sherwood (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

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Abstract

Aberrant regulation of WNT/β-catenin signaling plays 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, 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.

Original language	English
Pages (from-to)	3119-3136
Number of pages	18
Journal	Oncogene
Volume	36
Issue number	22
Early online date	16 Jan 2017
DOIs	https://doi.org/10.1038/onc.2016.450
Publication status	Published - 1 Jun 2017

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Final published version, 4.73 MBLicence: CC BY

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@article{b7e022b5978947628c3e08ed544e5073,

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 plays 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, 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. ",

author = "Kate Brown and Peggy Yang and \{Nobre Salvador\}, Daniela and Rima Kulikauskas and Hannele Ruohola-Baker and Robitaille, \{Aaron M.\} and Chien, \{Andy J.\} and Moon, \{Randall T.\} and Victoria Sherwood",

note = "This work was supported by start-up funding awarded to VS and grants from the Royal Society, London, and the British Skin Foundation (also awarded to VS). VS is supported by a CRUK program grant awarded to the CRUK-STL, School of Medicine, University of Dundee. RTM is an investigator of the Howard Hughes Medical Institute, which partially funded this work. This work was supported in part by the University of Washington{\textquoteright}s Proteomics Resource (UWPR95794).",

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doi = "10.1038/onc.2016.450",

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T1 - WNT/β-catenin signaling regulates mitochondrial activity to alter the oncogenic potential of melanoma in a PTEN-dependent manner

AU - Brown, Kate

AU - Yang, Peggy

AU - Nobre Salvador, Daniela

AU - Kulikauskas, Rima

AU - Ruohola-Baker, Hannele

AU - Robitaille, Aaron M.

AU - Chien, Andy J.

AU - Moon, Randall T.

AU - Sherwood, Victoria

N1 - This work was supported by start-up funding awarded to VS and grants from the Royal Society, London, and the British Skin Foundation (also awarded to VS). VS is supported by a CRUK program grant awarded to the CRUK-STL, School of Medicine, University of Dundee. RTM is an investigator of the Howard Hughes Medical Institute, which partially funded this work. This work was supported in part by the University of Washington’s Proteomics Resource (UWPR95794).

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Aberrant regulation of WNT/β-catenin signaling plays 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, 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.

AB - Aberrant regulation of WNT/β-catenin signaling plays 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, 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.

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JO - Oncogene

JF - Oncogene

IS - 22

ER -

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

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