Bmi1 Severs as a Potential Tumor-Initiating Cell Marker and Therapeutic Target in Esophageal Squamous Cell Carcinoma.

Xiaochen Wang,Hui Han,Liang Peng,Yong Bao,Kang Li,Demeng Chen,Wenjing Liao,Zhi Chen,Fangfang Chen,Maosheng Cheng,Ganping Wang,Jianwen Chen,Quan Yuan

doi:10.1155/2020/8877577

Abstract

Esophageal squamous cell carcinoma (ESCC) is a frequent malignant tumor with low 5-year overall survival. Targeting ESCC tumor-initiating cells (TICs) may provide a new research avenue to achieve better therapeutic effects of ESCC. However, the identity and characteristics of ESCC TICs remain poorly understood. Through genetic lineage tracing approach, we found that a group of Moloney murine leukemia virus insertion site 1- (Bmi1-) expressing cell populations present in the invasive front of the esophageal epithelium, providing a continuous flow of tumor cells for ESCC. Subsequently, we found that ablation of Bmi1+ cells from mice with ESCC led to inhibition of tumor growth. In addition, our results demonstrated that PTC-209, an inhibitor of Bmi1, was able to inhibit ESCC progression when combined with cisplatin. In summary, our data suggest that Bmi1+ cells serve as TICs in ESCC.

Highlights

Esophageal cancer is one of the most commonly diagnosed cancers, ranking the sixth cancer-related mortality worldwide [1]. It is mainly composed of two histological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC)
Studies have shown that tumor-initiating cells (TICs) or cancer stem cells are the main cause of tumor recurrence and metastasis [4, 5]
We found that (1) the gene ablation of Bmi1 led to increased apoptosis, decreased proliferation, and weakened stemness of ESCC; (2) the Bmi1+ tumor cells led to the progressive growth of epithelial clones and the Bmi1+ tumor cells were tumor-initiating cells in ESCC; and (3) the cisplatin combined with Bmi1 targeting drug could effectively inhibit tumor growth in ESCC

Summary

Introduction

Esophageal cancer is one of the most commonly diagnosed cancers, ranking the sixth cancer-related mortality worldwide [1]. It is mainly composed of two histological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Early diagnosis of ESCC is hard to achieve, resulting in a majority of the ESCC patients diagnosed at advanced stages. The five-year survival rate of ESCC patients remained around 10% owing to high recurrence and distant metastasis [3]. Studies have shown that tumor-initiating cells (TICs) or cancer stem cells are the main cause of tumor recurrence and metastasis [4, 5].

Methods

Discussion

Conclusion