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CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α

C–X–C motif chemokine receptor 4 (CXCR4) belongs to the CXC chemokine receptor family, which mediates the metastasis of tumor cells and promotes the malignant development of cancers. However, its biological role and regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. He...

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Autores principales: Wu, Xianxian, Zhang, Hongdian, Sui, Zhilin, Gao, Yongyin, Gong, Lei, Chen, Chuangui, Ma, Zhao, Tang, Peng, Yu, Zhentao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898735/
https://www.ncbi.nlm.nih.gov/pubmed/34990040
http://dx.doi.org/10.1111/cas.15265
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author Wu, Xianxian
Zhang, Hongdian
Sui, Zhilin
Gao, Yongyin
Gong, Lei
Chen, Chuangui
Ma, Zhao
Tang, Peng
Yu, Zhentao
author_facet Wu, Xianxian
Zhang, Hongdian
Sui, Zhilin
Gao, Yongyin
Gong, Lei
Chen, Chuangui
Ma, Zhao
Tang, Peng
Yu, Zhentao
author_sort Wu, Xianxian
collection PubMed
description C–X–C motif chemokine receptor 4 (CXCR4) belongs to the CXC chemokine receptor family, which mediates the metastasis of tumor cells and promotes the malignant development of cancers. However, its biological role and regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we found that CXCR4 expression was associated with lymph node metastasis and a poor prognosis. In vitro and in vivo studies demonstrated that CXCR4 overexpression promoted ESCC cell proliferation, migration, invasion, and survival, whereas silencing CXCR4 induced the opposite effects. Mechanically, HIF‐1α transcriptionally regulates CXCR4 expression by binding to a hypoxia response element in its promoter. HIF‐1α‐induced ESCC cell migration and invasion were reversed by CXCR4 knockdown or treatment with MSX‐122, a CXCR4 antagonist. Collectively, these data revealed that the HIF‐1α/CXCR4 axis plays key roles in ESCC growth and metastasis and indicated CXCR4 as a potential target for ESCC treatment.
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spelling pubmed-88987352022-03-11 CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α Wu, Xianxian Zhang, Hongdian Sui, Zhilin Gao, Yongyin Gong, Lei Chen, Chuangui Ma, Zhao Tang, Peng Yu, Zhentao Cancer Sci Original Articles C–X–C motif chemokine receptor 4 (CXCR4) belongs to the CXC chemokine receptor family, which mediates the metastasis of tumor cells and promotes the malignant development of cancers. However, its biological role and regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we found that CXCR4 expression was associated with lymph node metastasis and a poor prognosis. In vitro and in vivo studies demonstrated that CXCR4 overexpression promoted ESCC cell proliferation, migration, invasion, and survival, whereas silencing CXCR4 induced the opposite effects. Mechanically, HIF‐1α transcriptionally regulates CXCR4 expression by binding to a hypoxia response element in its promoter. HIF‐1α‐induced ESCC cell migration and invasion were reversed by CXCR4 knockdown or treatment with MSX‐122, a CXCR4 antagonist. Collectively, these data revealed that the HIF‐1α/CXCR4 axis plays key roles in ESCC growth and metastasis and indicated CXCR4 as a potential target for ESCC treatment. John Wiley and Sons Inc. 2022-01-17 2022-03 /pmc/articles/PMC8898735/ /pubmed/34990040 http://dx.doi.org/10.1111/cas.15265 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, 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 Original Articles
Wu, Xianxian
Zhang, Hongdian
Sui, Zhilin
Gao, Yongyin
Gong, Lei
Chen, Chuangui
Ma, Zhao
Tang, Peng
Yu, Zhentao
CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α
title CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α
title_full CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α
title_fullStr CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α
title_full_unstemmed CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α
title_short CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α
title_sort cxcr4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of hif‐1α
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898735/
https://www.ncbi.nlm.nih.gov/pubmed/34990040
http://dx.doi.org/10.1111/cas.15265
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