HIF-1–regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation

Significance Breast cancer stem cells (BCSCs) have the property of infinite self-renewal. When these cells divide, they give rise to one BCSC and one transient amplifying cell that can rapidly proliferate but only for a limited number of cell divisions. Only BCSCs can give rise to secondary (recurrent and/or metastatic) tumors. It is believed that breast cancer recurrence is due to the survival of a small number of BCSCs. Because the BCSCs represent a very small minority of cells within the primary tumor, their unique characteristics may not be detected by bulk tumor analyses. BCSCs are often located within regions of intratumoral hypoxia, and hypoxia-inducible factors activate the transcription of genes that promote BCSC specification and/or maintenance.