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Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis

The tumor microenvironment (TME) and Warburg effect are critical for the regulation of tumor metastasis. The monocarboxylate transporter (MCT) family members, particularly MCT4, which is encoded by the solute carrier family 16 member 3 gene, play an important role in the regulation of the TME and me...

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Autores principales: Zhou, Xiaoju, Wang, Shuo, Li, Yanyan, Zhao, He, Han, Xue, Yu, Yue, Chen, Yu, Yang, Yu, Ma, Xiaonan, Huo, Hongjing, Zhang, Manting, Zhao, Yongshan, Ma, Ningning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512108/
https://www.ncbi.nlm.nih.gov/pubmed/37745980
http://dx.doi.org/10.3892/ol.2023.14047
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author Zhou, Xiaoju
Wang, Shuo
Li, Yanyan
Zhao, He
Han, Xue
Yu, Yue
Chen, Yu
Yang, Yu
Ma, Xiaonan
Huo, Hongjing
Zhang, Manting
Zhao, Yongshan
Ma, Ningning
author_facet Zhou, Xiaoju
Wang, Shuo
Li, Yanyan
Zhao, He
Han, Xue
Yu, Yue
Chen, Yu
Yang, Yu
Ma, Xiaonan
Huo, Hongjing
Zhang, Manting
Zhao, Yongshan
Ma, Ningning
author_sort Zhou, Xiaoju
collection PubMed
description The tumor microenvironment (TME) and Warburg effect are critical for the regulation of tumor metastasis. The monocarboxylate transporter (MCT) family members, particularly MCT4, which is encoded by the solute carrier family 16 member 3 gene, play an important role in the regulation of the TME and mediation of the Warburg effect by transporting lactate out of cancer cells. Migration and invasion are two key features of metastasis. Few studies have investigated the mechanism by which MCT4 promotes cell migration, and the suggested mechanisms by which MCT4 promotes migration vary in different tumor cell models. The purpose of the present study was to use non-cancerous cells as a research model to investigate the specific mechanism underlying the promotion of migration by MCT4. In a previous study, murine L929 cells overexpressing human MCT4 (MCT4-L929 cells) were generated and MCT4 was demonstrated to promote the migration and invasion of these non-cancerous cells. In the present study, MCT4-L929 cells and control-L929 cells were used to investigate the potential pathways and mechanisms through which MCT4 promotes cell migration. RNA sequencing analysis revealed 872 differentially expressed genes, comprising 337 and 535 upregulated and downregulated genes, respectively, in the MCT4-L929 cells. Reverse transcription-quantitative analysis and western blotting revealed that MCT4 overexpression increased the transcription and protein levels of insulin-like growth factor 1 (IGF1). In a wound healing assay, the migration of exogenous mouse IGF1-treated control-L929 cells was similar to that of MCT4-L929 cells. Additionally, the inhibition of IGF1 receptor (IGF1R) or serum/glucocorticoid regulated kinase 1 (SGK1), a downstream protein in the IGF1 and phosphoinositide 3-kinase PI3K regulatory subunit 3 (PIK3R3) pathways, in MCT4-L929 cells mitigated the cell migration-promoting effect of MCT4. These novel findings suggest that MCT4 may promote the migration of L929 fibroblast cells via activation of the IGF1/IGF1R/PIK3R3/SGK1 axis.
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spelling pubmed-105121082023-09-22 Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis Zhou, Xiaoju Wang, Shuo Li, Yanyan Zhao, He Han, Xue Yu, Yue Chen, Yu Yang, Yu Ma, Xiaonan Huo, Hongjing Zhang, Manting Zhao, Yongshan Ma, Ningning Oncol Lett Articles The tumor microenvironment (TME) and Warburg effect are critical for the regulation of tumor metastasis. The monocarboxylate transporter (MCT) family members, particularly MCT4, which is encoded by the solute carrier family 16 member 3 gene, play an important role in the regulation of the TME and mediation of the Warburg effect by transporting lactate out of cancer cells. Migration and invasion are two key features of metastasis. Few studies have investigated the mechanism by which MCT4 promotes cell migration, and the suggested mechanisms by which MCT4 promotes migration vary in different tumor cell models. The purpose of the present study was to use non-cancerous cells as a research model to investigate the specific mechanism underlying the promotion of migration by MCT4. In a previous study, murine L929 cells overexpressing human MCT4 (MCT4-L929 cells) were generated and MCT4 was demonstrated to promote the migration and invasion of these non-cancerous cells. In the present study, MCT4-L929 cells and control-L929 cells were used to investigate the potential pathways and mechanisms through which MCT4 promotes cell migration. RNA sequencing analysis revealed 872 differentially expressed genes, comprising 337 and 535 upregulated and downregulated genes, respectively, in the MCT4-L929 cells. Reverse transcription-quantitative analysis and western blotting revealed that MCT4 overexpression increased the transcription and protein levels of insulin-like growth factor 1 (IGF1). In a wound healing assay, the migration of exogenous mouse IGF1-treated control-L929 cells was similar to that of MCT4-L929 cells. Additionally, the inhibition of IGF1 receptor (IGF1R) or serum/glucocorticoid regulated kinase 1 (SGK1), a downstream protein in the IGF1 and phosphoinositide 3-kinase PI3K regulatory subunit 3 (PIK3R3) pathways, in MCT4-L929 cells mitigated the cell migration-promoting effect of MCT4. These novel findings suggest that MCT4 may promote the migration of L929 fibroblast cells via activation of the IGF1/IGF1R/PIK3R3/SGK1 axis. D.A. Spandidos 2023-09-11 /pmc/articles/PMC10512108/ /pubmed/37745980 http://dx.doi.org/10.3892/ol.2023.14047 Text en Copyright: © Zhou et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhou, Xiaoju
Wang, Shuo
Li, Yanyan
Zhao, He
Han, Xue
Yu, Yue
Chen, Yu
Yang, Yu
Ma, Xiaonan
Huo, Hongjing
Zhang, Manting
Zhao, Yongshan
Ma, Ningning
Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis
title Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis
title_full Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis
title_fullStr Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis
title_full_unstemmed Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis
title_short Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis
title_sort monocarboxylate transporter 4 promotes the migration of non‑cancerous l929 fibroblast cells by activating the igf1/igf1r/pik3r3/sgk1 axis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512108/
https://www.ncbi.nlm.nih.gov/pubmed/37745980
http://dx.doi.org/10.3892/ol.2023.14047
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