Bmi-1 regulates snail expression and promotes metastasis ability in head and neck squamous cancer-derived ALDH1 positive cells

Abstract

Recent studies suggest that ALDH1 is a putative marker for HNSCC-derived cancer stem cells. However, the regulation mechanisms that maintain the stemness and metastatic capability of HNSCC- ALDH 1 + cells remain unclear. Initially, HNSCC- ALDH 1 + cells from HNSCC patient showed cancer stemness properties, and high expression of Bmi1 and Snail. Functionally, tumorigenic properties of HNSCC- ALDH 1 + cells could be downregulated by knockdown of Bmi-1. Overexpression of Bmi-1 altered in expression property ALDH 1 - cells to that of ALDH 1 + cells. Furthermore, knockdown of Bmi-1 enhanced the radiosensitivity of radiation-treated HNSCC- ALDH 1 + cells. Moreover, overexpression of Bmi-1 in HNSCC- ALDH 1 - cells increased tumor volume and number of pulmonary metastatic lesions by xenotransplant assay. Importantly, knock-down of Bmi1 in HNSCC- ALDH 1 + cells significantly decreased distant metastases in the lungs. Clinically, coexpression of Bmi-1/Snail/ALDH1 predicted the worst prognosis in HNSCC patients. Collectively, our data suggested that Bmi-1 plays a key role in regulating Snail expression and cancer stemness properties of HNSCC- ALDH 1 + cells. Copyright © 2011 Cheng-Chia Yu et al.