OV6(+) cancer stem cells drive esophageal squamous cell carcinoma progression through ATG7-dependent β-catenin stabilization.

Cancer stem cells (CSCs) represent a subpopulation of tumor cells that exhibit capacities for tumor initiation and progression. Identifying CSCs and their related pathways is necessary for the development of new therapeutic targets against tumors. However, the molecular mechanism of CSCs in esophageal squamous cell carcinoma (ESCC) remains elusive. This study demonstrated that OV6 expression was closely associated with ESCC patients' clinical outcome and prognosis. OV6(+) cells possessed stronger stem-like properties, including self-renewal, stem cell-associated gene expression, tumorigenicity, chemo-resistance, invasion, and metastasis. Autophagy maintained the stem-like properties of OV6(+) cells by stabilizing ATG7-dependent β-catenin. Furthermore, a significantly positive correlation between ATG7 and OV6 expression was detected in human ESCC biopsies, and this correlation could be used to predict ESCC patients' prognosis. Taken together, our findings provide a novel potential CSC marker for ESCC. OV6(+) cancer stem cells can promote the progression of ESCC through ATG7-dependent β-catenin stabilization. OV6 may serve as a novel prognostic biomarker and therapeutic target for ESCC patients.