Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of
esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells,
TIC) is inherently resistant to cytotoxic
chemotherapy and radiation and associates with poor prognosis and
therapy failure. Targeting
therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC
membrane protein markers using two distinct stemness characteristics of
cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses,
intercellular adhesion molecule 1 (ICAM1) was identified as a potential CSC marker of ESCC. ICAM1 promotes
cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and
tumorigenesis in mouse
xenotransplantation model. Based on the analysis of ICAM1-regulated
proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting
therapies should be under serious consideration to acquire a more potent
therapeutic effect on CSC of ESCC.