Regulated splicing of the ?6 integrin cytoplasmic domain determines the fate of breast cancer stem cells.

ABSTRACT: Although the ?6?1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two ?6 cytoplasmic domain splice variants: ?6A and ?6B. ?6B?1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by ?6A integrins. The generation of ?6B?1 is tightly controlled and occurs as a consequence of an autocrine vascular endothelial growth factor (VEGF) signaling that culminates in the transcriptional repression of a key RNA-splicing factor. These data alter our understanding of how ?6?1 contributes to breast cancer, and they resolve ambiguities regarding the use of total ?6 (CD49f) expression as a biomarker for CSCs.

SUBMITTER: Goel HL 

PROVIDER: S-EPMC4038359 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature