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Critical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells
Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non‐invasive and invasive potential, and microphthalmia‐associated transcription factor (MITF) is known to play a centra...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543504/ https://www.ncbi.nlm.nih.gov/pubmed/28635133 http://dx.doi.org/10.1111/cas.13294 |
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author | Gunarta, I Ketut Li, Rong Nakazato, Ryota Suzuki, Ryusuke Boldbaatar, Jambaldorj Suzuki, Takeshi Yoshioka, Katsuji |
author_facet | Gunarta, I Ketut Li, Rong Nakazato, Ryota Suzuki, Ryusuke Boldbaatar, Jambaldorj Suzuki, Takeshi Yoshioka, Katsuji |
author_sort | Gunarta, I Ketut |
collection | PubMed |
description | Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non‐invasive and invasive potential, and microphthalmia‐associated transcription factor (MITF) is known to play a central role in this process. The transcription factor glioma‐associated oncogene homolog 1 (GLI1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although GLI1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear. Here we investigated whether and how GLI1 is involved in the invasive ability of melanoma cells. Gli1 knockdown (KD) melanoma cell lines, established by using Gli1‐targeting lentiviral short hairpin RNA, exhibited a markedly reduced invasion ability, but their MITF expression and activity were the same as controls. Gli1 KD melanoma cells also led to less lung metastasis in mice compared with control melanoma cells. Furthermore, the Gli1 KD melanoma cells underwent a mesenchymal‐to‐epithelial‐like transition, accompanied by downregulation of the epithelial‐to‐mesenchymal transition (EMT)‐inducing transcription factors (EMT‐TF) Snail1, Zeb1 and Twist1, but not Snail2 or Zeb2. Collectively, these results indicate that GLI1 is important for maintaining the invasive and mesenchymal‐like properties of melanoma cells independent of MITF, most likely by modulating a subset of EMT‐TF. Our findings provide new insight into how heterogeneity and plasticity are achieved and regulated in melanoma. |
format | Online Article Text |
id | pubmed-5543504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-55435042017-08-09 Critical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells Gunarta, I Ketut Li, Rong Nakazato, Ryota Suzuki, Ryusuke Boldbaatar, Jambaldorj Suzuki, Takeshi Yoshioka, Katsuji Cancer Sci Original Articles Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non‐invasive and invasive potential, and microphthalmia‐associated transcription factor (MITF) is known to play a central role in this process. The transcription factor glioma‐associated oncogene homolog 1 (GLI1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although GLI1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear. Here we investigated whether and how GLI1 is involved in the invasive ability of melanoma cells. Gli1 knockdown (KD) melanoma cell lines, established by using Gli1‐targeting lentiviral short hairpin RNA, exhibited a markedly reduced invasion ability, but their MITF expression and activity were the same as controls. Gli1 KD melanoma cells also led to less lung metastasis in mice compared with control melanoma cells. Furthermore, the Gli1 KD melanoma cells underwent a mesenchymal‐to‐epithelial‐like transition, accompanied by downregulation of the epithelial‐to‐mesenchymal transition (EMT)‐inducing transcription factors (EMT‐TF) Snail1, Zeb1 and Twist1, but not Snail2 or Zeb2. Collectively, these results indicate that GLI1 is important for maintaining the invasive and mesenchymal‐like properties of melanoma cells independent of MITF, most likely by modulating a subset of EMT‐TF. Our findings provide new insight into how heterogeneity and plasticity are achieved and regulated in melanoma. John Wiley and Sons Inc. 2017-07-11 2017-08 /pmc/articles/PMC5543504/ /pubmed/28635133 http://dx.doi.org/10.1111/cas.13294 Text en © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Gunarta, I Ketut Li, Rong Nakazato, Ryota Suzuki, Ryusuke Boldbaatar, Jambaldorj Suzuki, Takeshi Yoshioka, Katsuji Critical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells |
title | Critical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells |
title_full | Critical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells |
title_fullStr | Critical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells |
title_full_unstemmed | Critical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells |
title_short | Critical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells |
title_sort | critical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543504/ https://www.ncbi.nlm.nih.gov/pubmed/28635133 http://dx.doi.org/10.1111/cas.13294 |
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