Identification and characterization of ITGA7 as cancer stem cell marker in esophageal squamous cell carcinoma (ESCC)

Abstract

Cancer stem cells (CSCs) are widely accepted as a specific subpopulation of cells responsible for cancer initiation and progression. CSCs have yet to be identified in ESCC that have an increasing incidence in developed countries. Our recent study in esophageal squamous cell carcinoma (ESCC) has led to the identification of ITGA7 as a functional CSCs marker. ITGA7+ cell population is endowed with stem cell-like properties and high tumorigenic and metastatic potential. ITGA7+ CSCs isolated from ESCC cell lines possessed higher self-renewal activity and were sufficient for tumor initiation, differentiation, and metastasis compared to ITGA7- ESCC cells. Functional studies using lentiviral-based overexpression and suppression systems demonstrated that ITGA7 can promote tumor initiation and metastasis through a deregulated FAK-Raf-MEK1/2-ERK signaling pathway and epithelial-mesenchymal transition. Further characterization of ITGA7+ population may provide a prognostic biomarker for ESCC outcome prediction and a potential therapeutic target.