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SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis

Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induce...

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Autores principales: Yao, Chenguang, Weng, Jun, Feng, Lingyun, Zhang, Wanjun, Xu, Yan, Zhang, Peijing, Tanaka, Yoshimasa, Su, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790513/
https://www.ncbi.nlm.nih.gov/pubmed/35096814
http://dx.doi.org/10.3389/fcell.2021.779169
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author Yao, Chenguang
Weng, Jun
Feng, Lingyun
Zhang, Wanjun
Xu, Yan
Zhang, Peijing
Tanaka, Yoshimasa
Su, Li
author_facet Yao, Chenguang
Weng, Jun
Feng, Lingyun
Zhang, Wanjun
Xu, Yan
Zhang, Peijing
Tanaka, Yoshimasa
Su, Li
author_sort Yao, Chenguang
collection PubMed
description Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induced proliferation-associated 1 (SIPA1) enhanced aerobic glycolysis and altered the main source of ATP production from oxidative phosphorylation to glycolysis in breast cancer cells. We revealed that SIPA1 promoted the transcription of EPAS1, which is known as the gene encoding hypoxia-inducible factor-2α (HIF-2α) and up-regulated the expression of multiple glycolysis-related genes to increase aerobic glycolysis. We also found that blocking aerobic glycolysis by either knocking down SIPA1 expression or oxamate treatment led to the suppression of tumor metastasis of breast cancer cells both in vitro and in vivo. Taken together, aberrant expression of SIPA1 resulted in the alteration of glucose metabolism from oxidative phosphorylation to aerobic glycolysis even at ambient oxygen levels, which might aggravate the malignancy of breast cancer cells. The present findings indicate a potential target for the development of therapeutics against breast cancers with dysregulated SIPA1 expression.
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spelling pubmed-87905132022-01-27 SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis Yao, Chenguang Weng, Jun Feng, Lingyun Zhang, Wanjun Xu, Yan Zhang, Peijing Tanaka, Yoshimasa Su, Li Front Cell Dev Biol Cell and Developmental Biology Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induced proliferation-associated 1 (SIPA1) enhanced aerobic glycolysis and altered the main source of ATP production from oxidative phosphorylation to glycolysis in breast cancer cells. We revealed that SIPA1 promoted the transcription of EPAS1, which is known as the gene encoding hypoxia-inducible factor-2α (HIF-2α) and up-regulated the expression of multiple glycolysis-related genes to increase aerobic glycolysis. We also found that blocking aerobic glycolysis by either knocking down SIPA1 expression or oxamate treatment led to the suppression of tumor metastasis of breast cancer cells both in vitro and in vivo. Taken together, aberrant expression of SIPA1 resulted in the alteration of glucose metabolism from oxidative phosphorylation to aerobic glycolysis even at ambient oxygen levels, which might aggravate the malignancy of breast cancer cells. The present findings indicate a potential target for the development of therapeutics against breast cancers with dysregulated SIPA1 expression. Frontiers Media S.A. 2022-01-12 /pmc/articles/PMC8790513/ /pubmed/35096814 http://dx.doi.org/10.3389/fcell.2021.779169 Text en Copyright © 2022 Yao, Weng, Feng, Zhang, Xu, Zhang, Tanaka and Su. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Yao, Chenguang
Weng, Jun
Feng, Lingyun
Zhang, Wanjun
Xu, Yan
Zhang, Peijing
Tanaka, Yoshimasa
Su, Li
SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis
title SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis
title_full SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis
title_fullStr SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis
title_full_unstemmed SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis
title_short SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis
title_sort sipa1 enhances aerobic glycolysis through hif-2α pathway to promote breast cancer metastasis
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790513/
https://www.ncbi.nlm.nih.gov/pubmed/35096814
http://dx.doi.org/10.3389/fcell.2021.779169
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