Open AccessCXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF‐1α
Author(s) -
Wu Xianxian,
Zhang Hongdian,
Sui Zhilin,
Gao Yongyin,
Gong Lei,
Chen Chuangui,
Ma Zhao,
Tang Peng,
Yu Zhentao
Publication year - 2022
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15265
Subject(s) - cxcr4 , cancer research , cxc chemokine receptors , metastasis , chemokine receptor , cell migration , biology , gene knockdown , chemokine , mediator , gene silencing , cxcr4 antagonist , cell growth , in vivo , cell , cell culture , receptor , medicine , microbiology and biotechnology , cancer , biochemistry , genetics , gene
Abstract 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.