Nestin depletion induces melanoma matrix metalloproteinases and invasion
Matrix metalloproteinases (MMPs) are key biological mediators of processes as diverse as wound healing, embryogenesis, and cancer progression. Although MMPs may be induced through multiple signaling pathways, the precise mechanisms for their regulation in cancer are incompletely understood. Because...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419570/ https://www.ncbi.nlm.nih.gov/pubmed/25365206 http://dx.doi.org/10.1038/labinvest.2014.130 |
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author | Lee, Chung-Wei Zhan, Qian Lezcano, Cecilia Frank, Markus H. Huang, John Larson, Allison Lin, Jennifer Y. Wan, Marilyn T. Lin, Ping-I Ma, Jie Kleffel, Sonja Schatton, Tobias Lian, Christine G. Murphy, George F. |
author_facet | Lee, Chung-Wei Zhan, Qian Lezcano, Cecilia Frank, Markus H. Huang, John Larson, Allison Lin, Jennifer Y. Wan, Marilyn T. Lin, Ping-I Ma, Jie Kleffel, Sonja Schatton, Tobias Lian, Christine G. Murphy, George F. |
author_sort | Lee, Chung-Wei |
collection | PubMed |
description | Matrix metalloproteinases (MMPs) are key biological mediators of processes as diverse as wound healing, embryogenesis, and cancer progression. Although MMPs may be induced through multiple signaling pathways, the precise mechanisms for their regulation in cancer are incompletely understood. Because cytoskeletal changes are known to accompany MMP expression, we sought to examine the potential role of the poorly understood cytoskeletal protein, nestin, in modulating melanoma MMPs. Nestin knockdown (KD) upregulated expression of specific MMPs and MMP-dependent invasion both through extracellular matrix barriers in vitro and in peritumoral connective tissue of xenografts in vivo. Development of 3-dimensionsal melanospheres that in vitro partially recapitulate non-invasive tumorigenic melanoma growth was inhibited by nestin KD, although ECM invasion by aberrant melanospheres that did form was enhanced. Mechanistically, nestin KD-dependent melanoma invasion was associated with intracellular redistribution of phosphorylated focal adhesion kinase (pFAK) and increased melanoma cell responsiveness to transforming growth factor-beta (TGF-β), both implicated in pathways of melanoma invasion. The results suggest that the heretofore poorly understood intermediate filament, nestin, may serve as a novel mediator of MMPs critical to melanoma virulence. |
format | Online Article Text |
id | pubmed-4419570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-44195702015-06-01 Nestin depletion induces melanoma matrix metalloproteinases and invasion Lee, Chung-Wei Zhan, Qian Lezcano, Cecilia Frank, Markus H. Huang, John Larson, Allison Lin, Jennifer Y. Wan, Marilyn T. Lin, Ping-I Ma, Jie Kleffel, Sonja Schatton, Tobias Lian, Christine G. Murphy, George F. Lab Invest Article Matrix metalloproteinases (MMPs) are key biological mediators of processes as diverse as wound healing, embryogenesis, and cancer progression. Although MMPs may be induced through multiple signaling pathways, the precise mechanisms for their regulation in cancer are incompletely understood. Because cytoskeletal changes are known to accompany MMP expression, we sought to examine the potential role of the poorly understood cytoskeletal protein, nestin, in modulating melanoma MMPs. Nestin knockdown (KD) upregulated expression of specific MMPs and MMP-dependent invasion both through extracellular matrix barriers in vitro and in peritumoral connective tissue of xenografts in vivo. Development of 3-dimensionsal melanospheres that in vitro partially recapitulate non-invasive tumorigenic melanoma growth was inhibited by nestin KD, although ECM invasion by aberrant melanospheres that did form was enhanced. Mechanistically, nestin KD-dependent melanoma invasion was associated with intracellular redistribution of phosphorylated focal adhesion kinase (pFAK) and increased melanoma cell responsiveness to transforming growth factor-beta (TGF-β), both implicated in pathways of melanoma invasion. The results suggest that the heretofore poorly understood intermediate filament, nestin, may serve as a novel mediator of MMPs critical to melanoma virulence. 2014-11-03 2014-12 /pmc/articles/PMC4419570/ /pubmed/25365206 http://dx.doi.org/10.1038/labinvest.2014.130 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Lee, Chung-Wei Zhan, Qian Lezcano, Cecilia Frank, Markus H. Huang, John Larson, Allison Lin, Jennifer Y. Wan, Marilyn T. Lin, Ping-I Ma, Jie Kleffel, Sonja Schatton, Tobias Lian, Christine G. Murphy, George F. Nestin depletion induces melanoma matrix metalloproteinases and invasion |
title | Nestin depletion induces melanoma matrix metalloproteinases and invasion |
title_full | Nestin depletion induces melanoma matrix metalloproteinases and invasion |
title_fullStr | Nestin depletion induces melanoma matrix metalloproteinases and invasion |
title_full_unstemmed | Nestin depletion induces melanoma matrix metalloproteinases and invasion |
title_short | Nestin depletion induces melanoma matrix metalloproteinases and invasion |
title_sort | nestin depletion induces melanoma matrix metalloproteinases and invasion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419570/ https://www.ncbi.nlm.nih.gov/pubmed/25365206 http://dx.doi.org/10.1038/labinvest.2014.130 |
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