ITGA6 is directly regulated by hypoxia-inducible factors and enriches for cancer stem cell activity and invasion in metastatic breast cancer models.

Hypoxia-inducible factors (HIFs) are well-established mediators of tumor growth， the epithelial to mesenchymal transition (EMT) and metastasis. In several types of solid tumors， including breast cancers， the HIFs play a critical role in maintaining cancer stem cell (CSC) activity. Thus， we hypothesized that HIFs may also regulate transcription of markers of breast CSC activity. One approach to enrich for breast cells with stem-like phenotypes is FACS sorting， in which sub-populations of live cells are gated based on the expression of cell surface antigens， including various integrin subunits. Integrin alpha 6 (ITGA6; CD49f) is routinely used in combination with other integrin subunits to enrich for breast stem cells by FACS. Integrins not only mediate interactions with the extracellular matrix (ECM)， but also drive intracellular signaling events that communicate from the tumor microenvironment to inside of the tumor cell to alter phenotypes including migration and invasion.