Regulated splicing of the alpha6 integrin cytoplasmic domain determines the fate of breast cancer stem cells
AuthorsGoel, Hira Lal
Shultz, Leonard D.
Greiner, Dale L.
Norum, Jens Henrik
Shaw, Leslie M.
Mercurio, Arthur M.
KeywordsAmino Acids, Peptides, and Proteins
Skin and Connective Tissue Diseases
MetadataShow full item record
AbstractAlthough the alpha6beta1 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 alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 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 alpha6beta1 contributes to breast cancer, and they resolve ambiguities regarding the use of total alpha6 (CD49f) expression as a biomarker for CSCs.
Cell Rep. 2014 May 8;7(3):747-61. doi: 10.1016/j.celrep.2014.03.059. Epub 2014 Apr 24. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/26301
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/3.0/