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HIF1α Regulates IL17 Signaling Pathway Influencing Sensitivity of Taxane-Based Chemotherapy for Breast Cancer

Hypoxia-induced chemotherapy resistance is the main hindrance for solid tumor treatment. Hypoxia inducible factor-1α (HIF1α), an adaptive gene of hypoxia condition, played an important role in affecting chemotherapy sensitivity for many cancer types and various therapeutic regimens. This study focus...

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Autores principales: Dai, Huijuan, Sheng, Xiaonan, Wang, Yaohui, Zhou, Liheng, Lin, Yanping, Du, Yueyao, Yang, Fan, Sha, Rui, Peng, Jing, Yao, Linli, Yin, Wenjin, Lu, Jinsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476907/
https://www.ncbi.nlm.nih.gov/pubmed/34595177
http://dx.doi.org/10.3389/fcell.2021.729965
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author Dai, Huijuan
Sheng, Xiaonan
Wang, Yaohui
Zhou, Liheng
Lin, Yanping
Du, Yueyao
Yang, Fan
Sha, Rui
Peng, Jing
Yao, Linli
Yin, Wenjin
Lu, Jinsong
author_facet Dai, Huijuan
Sheng, Xiaonan
Wang, Yaohui
Zhou, Liheng
Lin, Yanping
Du, Yueyao
Yang, Fan
Sha, Rui
Peng, Jing
Yao, Linli
Yin, Wenjin
Lu, Jinsong
author_sort Dai, Huijuan
collection PubMed
description Hypoxia-induced chemotherapy resistance is the main hindrance for solid tumor treatment. Hypoxia inducible factor-1α (HIF1α), an adaptive gene of hypoxia condition, played an important role in affecting chemotherapy sensitivity for many cancer types and various therapeutic regimens. This study focused on the impact of HIF1α on predicting response and survival of taxane-based neoadjuvant therapy (NAT) for breast cancer (BC) patients and the concrete mechanism that HIF1α mediated paclitaxel chemo-insensitivity. We evaluated HIF1α expression immunohistochemically from biopsies of 108 BC patients receiving paclitaxel–cisplatin NAT. Univariate and multivariate logistic regression analysis revealed that high HIF1α expression led to lower rate of pathological complete response (pCR) and worse prognosis. Analysis of GEO datasets also indicated negative association between HIF1α expression and response of taxane-based NAT in BC patients. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of differential expression genes (DEGs) in different HIF1α expression groups from TCGA database showed that HIF1α participated in interleukin 17 (IL-17) signaling pathway. Correlation analysis suggested that HIF1α was positively related to the IL-17 pathway. CXC motif chemokine ligand 10 (CXCL10) was the only DEG in the IL-17 pathway inversely relating to NAT response. Experiments in vitro verified that HIF1α/IL-17 pathway influences paclitaxel sensitivity to BC cells. Correlation analysis between HIF1α/IL-17A/CXCL10 and infiltration of immune cells in BC uncovered that high expression of all the above three genes were positively correlated to neutrophil infiltration in BC. Collectively, our findings shed novel insight into the mechanism of chemotherapy resistance and implied that HIF1α inhibitor may be a promising drug combined with traditional chemotherapeutic drug to increase the chemotherapy efficacy.
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spelling pubmed-84769072021-09-29 HIF1α Regulates IL17 Signaling Pathway Influencing Sensitivity of Taxane-Based Chemotherapy for Breast Cancer Dai, Huijuan Sheng, Xiaonan Wang, Yaohui Zhou, Liheng Lin, Yanping Du, Yueyao Yang, Fan Sha, Rui Peng, Jing Yao, Linli Yin, Wenjin Lu, Jinsong Front Cell Dev Biol Cell and Developmental Biology Hypoxia-induced chemotherapy resistance is the main hindrance for solid tumor treatment. Hypoxia inducible factor-1α (HIF1α), an adaptive gene of hypoxia condition, played an important role in affecting chemotherapy sensitivity for many cancer types and various therapeutic regimens. This study focused on the impact of HIF1α on predicting response and survival of taxane-based neoadjuvant therapy (NAT) for breast cancer (BC) patients and the concrete mechanism that HIF1α mediated paclitaxel chemo-insensitivity. We evaluated HIF1α expression immunohistochemically from biopsies of 108 BC patients receiving paclitaxel–cisplatin NAT. Univariate and multivariate logistic regression analysis revealed that high HIF1α expression led to lower rate of pathological complete response (pCR) and worse prognosis. Analysis of GEO datasets also indicated negative association between HIF1α expression and response of taxane-based NAT in BC patients. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of differential expression genes (DEGs) in different HIF1α expression groups from TCGA database showed that HIF1α participated in interleukin 17 (IL-17) signaling pathway. Correlation analysis suggested that HIF1α was positively related to the IL-17 pathway. CXC motif chemokine ligand 10 (CXCL10) was the only DEG in the IL-17 pathway inversely relating to NAT response. Experiments in vitro verified that HIF1α/IL-17 pathway influences paclitaxel sensitivity to BC cells. Correlation analysis between HIF1α/IL-17A/CXCL10 and infiltration of immune cells in BC uncovered that high expression of all the above three genes were positively correlated to neutrophil infiltration in BC. Collectively, our findings shed novel insight into the mechanism of chemotherapy resistance and implied that HIF1α inhibitor may be a promising drug combined with traditional chemotherapeutic drug to increase the chemotherapy efficacy. Frontiers Media S.A. 2021-09-14 /pmc/articles/PMC8476907/ /pubmed/34595177 http://dx.doi.org/10.3389/fcell.2021.729965 Text en Copyright © 2021 Dai, Sheng, Wang, Zhou, Lin, Du, Yang, Sha, Peng, Yao, Yin and Lu. 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
Dai, Huijuan
Sheng, Xiaonan
Wang, Yaohui
Zhou, Liheng
Lin, Yanping
Du, Yueyao
Yang, Fan
Sha, Rui
Peng, Jing
Yao, Linli
Yin, Wenjin
Lu, Jinsong
HIF1α Regulates IL17 Signaling Pathway Influencing Sensitivity of Taxane-Based Chemotherapy for Breast Cancer
title HIF1α Regulates IL17 Signaling Pathway Influencing Sensitivity of Taxane-Based Chemotherapy for Breast Cancer
title_full HIF1α Regulates IL17 Signaling Pathway Influencing Sensitivity of Taxane-Based Chemotherapy for Breast Cancer
title_fullStr HIF1α Regulates IL17 Signaling Pathway Influencing Sensitivity of Taxane-Based Chemotherapy for Breast Cancer
title_full_unstemmed HIF1α Regulates IL17 Signaling Pathway Influencing Sensitivity of Taxane-Based Chemotherapy for Breast Cancer
title_short HIF1α Regulates IL17 Signaling Pathway Influencing Sensitivity of Taxane-Based Chemotherapy for Breast Cancer
title_sort hif1α regulates il17 signaling pathway influencing sensitivity of taxane-based chemotherapy for breast cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476907/
https://www.ncbi.nlm.nih.gov/pubmed/34595177
http://dx.doi.org/10.3389/fcell.2021.729965
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