Chloroquine Inhibits Stemness of Esophageal Squamous Cell Carcinoma Cells Through Targeting CXCR4-STAT3 Pathway

Dongli Yue; Daiqun Zhang; Xiaojuan Shi; Shasha Liu; Anqi Li; Dong Wang; Guohui Qin; Yu Ping; Yamin Qiao; Xinfeng Chen; Feng Wang; Renyin Chen; Song Zhao; Lidong Wang; Yi Zhang

doi:10.3389/fonc.2020.00311

Chloroquine Inhibits Stemness of Esophageal Squamous Cell Carcinoma Cells Through Targeting CXCR4-STAT3 Pathway

Front Oncol. 2020 Mar 13:10:311. doi: 10.3389/fonc.2020.00311. eCollection 2020.

Authors

Dongli Yue^{1

2}, Daiqun Zhang¹, Xiaojuan Shi¹, Shasha Liu¹, Anqi Li¹, Dong Wang^{1

2}, Guohui Qin^{1

2}, Yu Ping¹, Yamin Qiao^{1

2}, Xinfeng Chen^{1

2}, Feng Wang², Renyin Chen³, Song Zhao⁴, Lidong Wang⁵, Yi Zhang^{1

6

7}

Affiliations

¹ Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁴ Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁵ Henan Key Laboratory for Esophageal Cancer Research and State Key Laboratory for Esophageal Cancer Prevention & Treatment of The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁶ School of Life Sciences, Zhengzhou University, Zhengzhou, China.
⁷ Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, China.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide. Recent studies have shown that cancer stem cells (CSCs) are present in ESCC, are thought to lead to aggressive tumor behavior and the prognosis. The CXC chemokine receptor 4 (CXCR4), is regarded as a putative CSCs marker in various malignancies. Here, we demonstrate that CXCR4 played a key role in ESCC progression and CXCR4 positive ESCC cells possessed stem-like properties. Furthermore, the anti-malarial agent chloroquine (CQ) targeted CXCR4-positive ESCC cells via STAT3 pathway. Therefore, CQ with anti-CSCs effects may be an effective adjunct to current ESCC chemotherapy regimens.

Keywords: CXCR4; STAT3; cancer stem cells (CSCs); chloroquine (CQ); esophageal squamous cell carcinoma (ESCC).