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

K Brown; P Yang; D Salvador; R Kulikauskas; H Ruohola-Baker; A M Robitaille; A J Chien; R T Moon; V 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

K Brown, P Yang, D Salvador, R Kulikauskas, H Ruohola-Baker, A M Robitaille, A J Chien, R T Moon, V Sherwood

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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.

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

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10.1038/onc.2016.450Licence: CC BY

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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Final published version, 4.16 MBLicence: CC BY

https://www.nature.com/onc/journal/v36/n22/full/onc2016450a.htmlLicence: CC BY

Development of multifunctional targeted drug nanocarriers for the treatment of metastatic melanoma
Baldelli Bombelli, F. & Sherwood, V.
British Skin Foundation (The)
1/01/13 → 31/12/14
Project: Research
Wnt Signalling Effects on Cancer Cell Bioenergetics and Mitochondrial Physiology
Sherwood, V. & Chien, A.
Royal Society
14/11/11 → 14/11/14
Project: Research
The effect of Wnt3a on melanoma cell mitochondria and energy metabolism
Sherwood, V.
Royal Society
1/11/11 → 31/10/12
Project: Research

Cite this

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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.",

author = "K Brown and P Yang and D Salvador and R Kulikauskas and H Ruohola-Baker and Robitaille, {A M} and Chien, {A J} and Moon, {R T} and V Sherwood",

year = "2017",

doi = "10.1038/onc.2016.450",

language = "English",

volume = "36",

pages = "3119–3136",

journal = "Oncogene",

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AU - Brown, K

AU - Yang, P

AU - Salvador, D

AU - Kulikauskas, R

AU - Ruohola-Baker, H

AU - Robitaille, A M

AU - Chien, A J

AU - Moon, R T

AU - Sherwood, V

PY - 2017

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AB - 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.

U2 - 10.1038/onc.2016.450

DO - 10.1038/onc.2016.450

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JO - Oncogene

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SN - 0950-9232

ER -

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

Abstract

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Projects

Development of multifunctional targeted drug nanocarriers for the treatment of metastatic melanoma

Wnt Signalling Effects on Cancer Cell Bioenergetics and Mitochondrial Physiology

The effect of Wnt3a on melanoma cell mitochondria and energy metabolism

Cite this