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A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions

Monocarboxylate transporters (MCTs) play an immense role in metabolically active solid tumors by regulating concentration-dependent transport of different important monocarboxylates including pyruvate and lactate and are encoded by the SLC16A family of genes. Given the vast array of functions, these...

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Autores principales: Chatterjee, Priti, Bhowmik, Debaleena, Roy, Sib Sankar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10631444/
https://www.ncbi.nlm.nih.gov/pubmed/37934721
http://dx.doi.org/10.1080/19336950.2023.2273008
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author Chatterjee, Priti
Bhowmik, Debaleena
Roy, Sib Sankar
author_facet Chatterjee, Priti
Bhowmik, Debaleena
Roy, Sib Sankar
author_sort Chatterjee, Priti
collection PubMed
description Monocarboxylate transporters (MCTs) play an immense role in metabolically active solid tumors by regulating concentration-dependent transport of different important monocarboxylates including pyruvate and lactate and are encoded by the SLC16A family of genes. Given the vast array of functions, these transporters play in oncogenesis, our objective was to look into the association of MCT1 (SLC16A1), MCT2 (SLC16A7), MCT3 (SLC16A8), and MCT4 (SLC16A3) with Epithelial ovarian cancer (EOC) pathophysiology by exploiting various publicly available databases and web resources. Few of the in silico findings were confirmed via in vitro experiments in EOC cell lines, SKOV3 and OAW-42. MCT1 and MCT4 were found to be upregulated at the mRNA level in OC tissues compared to normal. However, only higher level of MCT4 mRNA was found to be associated with poor patient survival. MCT4 was positively correlated with gene families responsible for invasion, migration, and immune modification, proving it to be one of the most important MCTs for therapeutic intervention. We compared the effects of MCT1/2 blocker SR13800 and a broad-spectrum MCT blocker α-Cyano Hydroxy Cinnamic Acid (α-CHCA) and discovered that α-CHCA has a greater effect on diminishing the invasive behavior of the cancer cells than MCT1/2 blocker SR13800. From our study, MCT4 has emerged as a prospective marker for predicting poor patient outcomes and a potential therapeutic target.
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spelling pubmed-106314442023-11-07 A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions Chatterjee, Priti Bhowmik, Debaleena Roy, Sib Sankar Channels (Austin) Research Paper Monocarboxylate transporters (MCTs) play an immense role in metabolically active solid tumors by regulating concentration-dependent transport of different important monocarboxylates including pyruvate and lactate and are encoded by the SLC16A family of genes. Given the vast array of functions, these transporters play in oncogenesis, our objective was to look into the association of MCT1 (SLC16A1), MCT2 (SLC16A7), MCT3 (SLC16A8), and MCT4 (SLC16A3) with Epithelial ovarian cancer (EOC) pathophysiology by exploiting various publicly available databases and web resources. Few of the in silico findings were confirmed via in vitro experiments in EOC cell lines, SKOV3 and OAW-42. MCT1 and MCT4 were found to be upregulated at the mRNA level in OC tissues compared to normal. However, only higher level of MCT4 mRNA was found to be associated with poor patient survival. MCT4 was positively correlated with gene families responsible for invasion, migration, and immune modification, proving it to be one of the most important MCTs for therapeutic intervention. We compared the effects of MCT1/2 blocker SR13800 and a broad-spectrum MCT blocker α-Cyano Hydroxy Cinnamic Acid (α-CHCA) and discovered that α-CHCA has a greater effect on diminishing the invasive behavior of the cancer cells than MCT1/2 blocker SR13800. From our study, MCT4 has emerged as a prospective marker for predicting poor patient outcomes and a potential therapeutic target. Taylor & Francis 2023-11-07 /pmc/articles/PMC10631444/ /pubmed/37934721 http://dx.doi.org/10.1080/19336950.2023.2273008 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Paper
Chatterjee, Priti
Bhowmik, Debaleena
Roy, Sib Sankar
A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions
title A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions
title_full A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions
title_fullStr A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions
title_full_unstemmed A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions
title_short A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions
title_sort systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10631444/
https://www.ncbi.nlm.nih.gov/pubmed/37934721
http://dx.doi.org/10.1080/19336950.2023.2273008
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