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The Role of the Hippo Pathway in Melanocytes and Melanoma

The Hippo signaling pathway comprises a series of cytoplasmic tumor suppressor proteins including Merlin and the Lats1/2 and MST1/2 kinases, and is thought to play a critical role in determining the sizes of organs and tissues. The Hippo pathway is regulated upstream by extracellular mechanosensory...

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Autores principales: Kim, Ji Eun, Finlay, Graeme J., Baguley, Bruce C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655322/
https://www.ncbi.nlm.nih.gov/pubmed/23720711
http://dx.doi.org/10.3389/fonc.2013.00123
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author Kim, Ji Eun
Finlay, Graeme J.
Baguley, Bruce C.
author_facet Kim, Ji Eun
Finlay, Graeme J.
Baguley, Bruce C.
author_sort Kim, Ji Eun
collection PubMed
description The Hippo signaling pathway comprises a series of cytoplasmic tumor suppressor proteins including Merlin and the Lats1/2 and MST1/2 kinases, and is thought to play a critical role in determining the sizes of organs and tissues. The Hippo pathway is regulated upstream by extracellular mechanosensory signaling arising from cell shape and polarity, as well as by a variety of extracellular signaling molecules. When active, the pathway maintains the transcriptional activators Yes-associated protein (YAP) and TAZ in phosphorylated forms in the cytoplasm, preventing cell proliferation. When the Hippo pathway is inactivated, YAP and TAZ are translocated to the nucleus and induce the expression of a variety of proteins concerned with entry into the cell division cycle, such as cyclin D1 and Fox M1, as well as the inhibition of apoptosis. The failure of the Hippo pathway has been implicated in the development of many different types of cancer but there is limited information available as to its involvement in melanoma. We hypothesize here firstly that the Hippo pathway is involved in maintaining density of cutaneous melanocytes on the basement membrane at the junction of the epidermis and the dermis, and secondly, that its function is disturbed in melanoma. We have analyzed a series of 23 low passage human melanoma lines as well as cultured normal melanoma, and find that melanocytes, as well as all melanoma cell lines examined express TAZ. Melanocytes and most melanoma lines also express YAP. E-cadherin, an upstream regulator of the Hippo pathway, and Axl, a receptor tyrosine kinase regulated by the Hippo pathway, are expressed in melanocytes and in several melanoma cell lines. These observations, together with published evidence for the presence of Merlin, Lats1/2, and MST1/2 in melanocytes and melanoma cells, support the hypothesis that the Hippo pathway is an important component of melanocyte and melanoma behavior.
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spelling pubmed-36553222013-05-29 The Role of the Hippo Pathway in Melanocytes and Melanoma Kim, Ji Eun Finlay, Graeme J. Baguley, Bruce C. Front Oncol Oncology The Hippo signaling pathway comprises a series of cytoplasmic tumor suppressor proteins including Merlin and the Lats1/2 and MST1/2 kinases, and is thought to play a critical role in determining the sizes of organs and tissues. The Hippo pathway is regulated upstream by extracellular mechanosensory signaling arising from cell shape and polarity, as well as by a variety of extracellular signaling molecules. When active, the pathway maintains the transcriptional activators Yes-associated protein (YAP) and TAZ in phosphorylated forms in the cytoplasm, preventing cell proliferation. When the Hippo pathway is inactivated, YAP and TAZ are translocated to the nucleus and induce the expression of a variety of proteins concerned with entry into the cell division cycle, such as cyclin D1 and Fox M1, as well as the inhibition of apoptosis. The failure of the Hippo pathway has been implicated in the development of many different types of cancer but there is limited information available as to its involvement in melanoma. We hypothesize here firstly that the Hippo pathway is involved in maintaining density of cutaneous melanocytes on the basement membrane at the junction of the epidermis and the dermis, and secondly, that its function is disturbed in melanoma. We have analyzed a series of 23 low passage human melanoma lines as well as cultured normal melanoma, and find that melanocytes, as well as all melanoma cell lines examined express TAZ. Melanocytes and most melanoma lines also express YAP. E-cadherin, an upstream regulator of the Hippo pathway, and Axl, a receptor tyrosine kinase regulated by the Hippo pathway, are expressed in melanocytes and in several melanoma cell lines. These observations, together with published evidence for the presence of Merlin, Lats1/2, and MST1/2 in melanocytes and melanoma cells, support the hypothesis that the Hippo pathway is an important component of melanocyte and melanoma behavior. Frontiers Media S.A. 2013-05-16 /pmc/articles/PMC3655322/ /pubmed/23720711 http://dx.doi.org/10.3389/fonc.2013.00123 Text en Copyright © 2013 Kim, Finlay and Baguley. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Oncology
Kim, Ji Eun
Finlay, Graeme J.
Baguley, Bruce C.
The Role of the Hippo Pathway in Melanocytes and Melanoma
title The Role of the Hippo Pathway in Melanocytes and Melanoma
title_full The Role of the Hippo Pathway in Melanocytes and Melanoma
title_fullStr The Role of the Hippo Pathway in Melanocytes and Melanoma
title_full_unstemmed The Role of the Hippo Pathway in Melanocytes and Melanoma
title_short The Role of the Hippo Pathway in Melanocytes and Melanoma
title_sort role of the hippo pathway in melanocytes and melanoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655322/
https://www.ncbi.nlm.nih.gov/pubmed/23720711
http://dx.doi.org/10.3389/fonc.2013.00123
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