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NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells
Na(+)/H(+) exchanger 5 (NHE5) is enriched in neurons and cycles between recycling endosomes and plasma membranes and transports protons to the endosomal lumen as well as to the extracellular space. Although NHE5 expression is undetectable in normal astrocytes, C6 glioma cells express NHE5 at an elev...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834540/ https://www.ncbi.nlm.nih.gov/pubmed/31595389 http://dx.doi.org/10.1007/s10585-019-10001-6 |
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author | Kurata, Toru Rajendran, Vinotheni Fan, Steven Ohta, Tetsuo Numata, Masayuki Fushida, Sachio |
author_facet | Kurata, Toru Rajendran, Vinotheni Fan, Steven Ohta, Tetsuo Numata, Masayuki Fushida, Sachio |
author_sort | Kurata, Toru |
collection | PubMed |
description | Na(+)/H(+) exchanger 5 (NHE5) is enriched in neurons and cycles between recycling endosomes and plasma membranes and transports protons to the endosomal lumen as well as to the extracellular space. Although NHE5 expression is undetectable in normal astrocytes, C6 glioma cells express NHE5 at an elevated level. Using C6 cells as a model, here we demonstrate that NHE5 has an important role in tumor growth and tumor cell proliferation and invasion. Glioma xenografts originating from NHE5-knockdown cells exhibited significantly slower growth than those from NHE1-knockdown cells and control cells. Histological characterization of the migration front of NHE5-knockdown tumors revealed a less invasive and less proliferative appearance than NHE1-knockdown and control tumors. NHE5-knockdown but not NHE1-knockdown led to downregulation of fetal bovine serum (FBS)-induced MET and EGFR signaling. Moreover, depletion of NHE5 but not NHE1 reduced the ability of cells to spread on collagen. We found that NHE5 depletion greatly abrogated endocytic recycling and the protein stability of β1-integrin, which in part accounted for the defective cell adhesion, spreading, and invasion of NHE5-knockdown cells. |
format | Online Article Text |
id | pubmed-6834540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-68345402019-11-20 NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells Kurata, Toru Rajendran, Vinotheni Fan, Steven Ohta, Tetsuo Numata, Masayuki Fushida, Sachio Clin Exp Metastasis Research Paper Na(+)/H(+) exchanger 5 (NHE5) is enriched in neurons and cycles between recycling endosomes and plasma membranes and transports protons to the endosomal lumen as well as to the extracellular space. Although NHE5 expression is undetectable in normal astrocytes, C6 glioma cells express NHE5 at an elevated level. Using C6 cells as a model, here we demonstrate that NHE5 has an important role in tumor growth and tumor cell proliferation and invasion. Glioma xenografts originating from NHE5-knockdown cells exhibited significantly slower growth than those from NHE1-knockdown cells and control cells. Histological characterization of the migration front of NHE5-knockdown tumors revealed a less invasive and less proliferative appearance than NHE1-knockdown and control tumors. NHE5-knockdown but not NHE1-knockdown led to downregulation of fetal bovine serum (FBS)-induced MET and EGFR signaling. Moreover, depletion of NHE5 but not NHE1 reduced the ability of cells to spread on collagen. We found that NHE5 depletion greatly abrogated endocytic recycling and the protein stability of β1-integrin, which in part accounted for the defective cell adhesion, spreading, and invasion of NHE5-knockdown cells. Springer Netherlands 2019-10-08 2019 /pmc/articles/PMC6834540/ /pubmed/31595389 http://dx.doi.org/10.1007/s10585-019-10001-6 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Paper Kurata, Toru Rajendran, Vinotheni Fan, Steven Ohta, Tetsuo Numata, Masayuki Fushida, Sachio NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells |
title | NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells |
title_full | NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells |
title_fullStr | NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells |
title_full_unstemmed | NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells |
title_short | NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells |
title_sort | nhe5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834540/ https://www.ncbi.nlm.nih.gov/pubmed/31595389 http://dx.doi.org/10.1007/s10585-019-10001-6 |
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