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GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge
The mechanism of directional cell migration remains an important problem, with relevance to cancer invasion and metastasis. GOLPH3 is a common oncogenic driver of human cancers, and is the first oncogene that functions at the Golgi in trafficking to the plasma membrane. Overexpression of GOLPH3 is r...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170606/ https://www.ncbi.nlm.nih.gov/pubmed/27708138 http://dx.doi.org/10.1091/mbc.E16-01-0005 |
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author | Xing, Mengke Peterman, Marshall C. Davis, Robert L. Oegema, Karen Shiau, Andrew K. Field, Seth J. |
author_facet | Xing, Mengke Peterman, Marshall C. Davis, Robert L. Oegema, Karen Shiau, Andrew K. Field, Seth J. |
author_sort | Xing, Mengke |
collection | PubMed |
description | The mechanism of directional cell migration remains an important problem, with relevance to cancer invasion and metastasis. GOLPH3 is a common oncogenic driver of human cancers, and is the first oncogene that functions at the Golgi in trafficking to the plasma membrane. Overexpression of GOLPH3 is reported to drive enhanced cell migration. Here we show that the phosphatidylinositol-4-phosphate/GOLPH3/myosin 18A/F-actin pathway that is critical for Golgi–to–plasma membrane trafficking is necessary and limiting for directional cell migration. By linking the Golgi to the actin cytoskeleton, GOLPH3 promotes reorientation of the Golgi toward the leading edge. GOLPH3 also promotes reorientation of lysosomes (but not other organelles) toward the leading edge. However, lysosome function is dispensable for migration and the GOLPH3 dependence of lysosome movement is indirect, via GOLPH3’s effect on the Golgi. By driving reorientation of the Golgi to the leading edge and driving forward trafficking, particularly to the leading edge, overexpression of GOLPH3 drives trafficking to the leading edge of the cell, which is functionally important for directional cell migration. Our identification of a novel pathway for Golgi reorientation controlled by GOLPH3 provides new insight into the mechanism of directional cell migration with important implications for understanding GOLPH3’s role in cancer. |
format | Online Article Text |
id | pubmed-5170606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-51706062017-02-16 GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge Xing, Mengke Peterman, Marshall C. Davis, Robert L. Oegema, Karen Shiau, Andrew K. Field, Seth J. Mol Biol Cell Articles The mechanism of directional cell migration remains an important problem, with relevance to cancer invasion and metastasis. GOLPH3 is a common oncogenic driver of human cancers, and is the first oncogene that functions at the Golgi in trafficking to the plasma membrane. Overexpression of GOLPH3 is reported to drive enhanced cell migration. Here we show that the phosphatidylinositol-4-phosphate/GOLPH3/myosin 18A/F-actin pathway that is critical for Golgi–to–plasma membrane trafficking is necessary and limiting for directional cell migration. By linking the Golgi to the actin cytoskeleton, GOLPH3 promotes reorientation of the Golgi toward the leading edge. GOLPH3 also promotes reorientation of lysosomes (but not other organelles) toward the leading edge. However, lysosome function is dispensable for migration and the GOLPH3 dependence of lysosome movement is indirect, via GOLPH3’s effect on the Golgi. By driving reorientation of the Golgi to the leading edge and driving forward trafficking, particularly to the leading edge, overexpression of GOLPH3 drives trafficking to the leading edge of the cell, which is functionally important for directional cell migration. Our identification of a novel pathway for Golgi reorientation controlled by GOLPH3 provides new insight into the mechanism of directional cell migration with important implications for understanding GOLPH3’s role in cancer. The American Society for Cell Biology 2016-12-01 /pmc/articles/PMC5170606/ /pubmed/27708138 http://dx.doi.org/10.1091/mbc.E16-01-0005 Text en © 2016 Xing, Peterman, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Xing, Mengke Peterman, Marshall C. Davis, Robert L. Oegema, Karen Shiau, Andrew K. Field, Seth J. GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge |
title | GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge |
title_full | GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge |
title_fullStr | GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge |
title_full_unstemmed | GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge |
title_short | GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge |
title_sort | golph3 drives cell migration by promoting golgi reorientation and directional trafficking to the leading edge |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170606/ https://www.ncbi.nlm.nih.gov/pubmed/27708138 http://dx.doi.org/10.1091/mbc.E16-01-0005 |
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