UMMS Affiliation

Department of Cancer Biology; Program in Molecular Medicine

Publication Date

2014-05-08

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cancer Biology | Cell Biology | Cells | Neoplasms | Skin and Connective Tissue Diseases

Abstract

Although 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.

DOI of Published Version

10.1016/j.celrep.2014.03.059

Source

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

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

24767994

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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