Hypoxia-induced ZEB1 Promotes Cervical Cancer Progression Via CCL8-dependent Tumour-associated Macrophage Recruitment

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2019 Jul 3

PMID 31263103

Citations 68

Authors

Xiao-Jing Chen

Yuan-Run Deng

Zi-Ci Wang

Wen-Fei Wei

Chen-Fei Zhou

Yan-Mei Zhang

Rui-Ming Yan

Luo-Jiao Liang

Mei Zhong

Li Liang

Sha Wu

Wei Wang

Affiliations

Soon will be listed here.

Abstract

The accumulation of tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is associated with malignant progression in cancer. However, the mechanisms by which the hypoxic TME facilitates TAM infiltration are not fully understood. This study showed that high ZEB1 expression in hypoxic cervical cancer cell islets was positively correlated with CD163 TAM accumulation. ZEB1 in hypoxic cancer cells promoted the migration of TAMs in vitro and altered the expression of multiple chemokines, especially CCL8. Mechanistically, hypoxia-induced ZEB1 activated the transcription of CCL8, which attracted macrophages via the CCR2-NF-κB pathway. Furthermore, ZEB1 and CCL8 were independent prognostic factors in cervical cancer patients based on The Cancer Genome Atlas (TCGA) data analysis. In conclusion, hypoxia-induced ZEB1 exerts unexpected functions in cancer progression by fostering a prometastatic environment through increased CCL8 secretion and TAM recruitment; thus, ZEB1 may serve as a candidate biomarker of tumour progression and provide a potential target for disrupting hypoxia-mediated TME remodelling.

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