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Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity
Tumor progression to metastatic disease contributes to the vast majority of incurable cancer. Understanding the processes leading to advanced stage cancer is important for the development of future therapeutic strategies. Here, we establish a connection between tumor cell migration, a prerequisite t...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078044/ https://www.ncbi.nlm.nih.gov/pubmed/27127175 http://dx.doi.org/10.18632/oncotarget.9016 |
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author | Gray, Alana L. Coleman, David T. Shi, Runhua Cardelli, James A. |
author_facet | Gray, Alana L. Coleman, David T. Shi, Runhua Cardelli, James A. |
author_sort | Gray, Alana L. |
collection | PubMed |
description | Tumor progression to metastatic disease contributes to the vast majority of incurable cancer. Understanding the processes leading to advanced stage cancer is important for the development of future therapeutic strategies. Here, we establish a connection between tumor cell migration, a prerequisite to metastasis, and monocarboxylate transporter 1 (MCT1). MCT1 transporter activity is known to regulate aspects of tumor progression and, as such, is a clinically relevant target for treating cancer. Knockdown of MCT1 expression caused decreased hepatocyte growth factor (HGF)-induced as well as epidermal growth factor (EGF)-induced tumor cell scattering and wound healing. Western blot analysis suggested that MCT1 knockdown (KD) hinders signaling through the HGF receptor (c-Met) but not the EGF receptor. Exogenous, membrane-permeable MCT1 substrates were not able to rescue motility in MCT1 KD cells, nor was pharmacologic inhibition of MCT1 able to recapitulate decreased cell motility as seen with MCT1 KD cells, indicating transporter activity of MCT1 was dispensable for EGF- and HGF-induced motility. These results indicate MCT1 expression, independent of transporter activity, is required for growth factor-induced tumor cell motility. The findings presented herein suggest a novel function for MCT1 in tumor progression independent of its role as a monocarboxylate transporter. |
format | Online Article Text |
id | pubmed-5078044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50780442016-10-28 Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity Gray, Alana L. Coleman, David T. Shi, Runhua Cardelli, James A. Oncotarget Research Paper Tumor progression to metastatic disease contributes to the vast majority of incurable cancer. Understanding the processes leading to advanced stage cancer is important for the development of future therapeutic strategies. Here, we establish a connection between tumor cell migration, a prerequisite to metastasis, and monocarboxylate transporter 1 (MCT1). MCT1 transporter activity is known to regulate aspects of tumor progression and, as such, is a clinically relevant target for treating cancer. Knockdown of MCT1 expression caused decreased hepatocyte growth factor (HGF)-induced as well as epidermal growth factor (EGF)-induced tumor cell scattering and wound healing. Western blot analysis suggested that MCT1 knockdown (KD) hinders signaling through the HGF receptor (c-Met) but not the EGF receptor. Exogenous, membrane-permeable MCT1 substrates were not able to rescue motility in MCT1 KD cells, nor was pharmacologic inhibition of MCT1 able to recapitulate decreased cell motility as seen with MCT1 KD cells, indicating transporter activity of MCT1 was dispensable for EGF- and HGF-induced motility. These results indicate MCT1 expression, independent of transporter activity, is required for growth factor-induced tumor cell motility. The findings presented herein suggest a novel function for MCT1 in tumor progression independent of its role as a monocarboxylate transporter. Impact Journals LLC 2016-04-26 /pmc/articles/PMC5078044/ /pubmed/27127175 http://dx.doi.org/10.18632/oncotarget.9016 Text en Copyright: © 2016 Gray et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Gray, Alana L. Coleman, David T. Shi, Runhua Cardelli, James A. Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity |
title | Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity |
title_full | Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity |
title_fullStr | Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity |
title_full_unstemmed | Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity |
title_short | Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity |
title_sort | monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078044/ https://www.ncbi.nlm.nih.gov/pubmed/27127175 http://dx.doi.org/10.18632/oncotarget.9016 |
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