Regulated Splicing of the α6 Integrin Cytoplasmic Domain Determines the Fate of Breast Cancer Stem Cells

• DOI: 10.1016/j.celrep.2014.03.059
• Publication Date: 2014-04-24T15:53:08Z
• Authors: Hira Lal Goel; Tatiana Gritsko; Bryan Pursell; Cheng Chang; Leonard D. Shultz; Dale L. Greiner; Jens Henrik Norum; Rune Toftgard; Leslie M. Shaw; Arthur M. Mercurio
• Keywords: Vascular Endothelial Growth Factor A; QH301-705.5; Cells; RNA Splicing; Breast Neoplasms; Integrin alpha6; Skin and Connective Tissue Diseases; Neoplasms; Cell Line, Tumor; Medicine and Health Sciences; Humans; Amino Acids; Biology (General); RNA, Small Interfering; Cancer Biology; Polycomb Repressive Complex 1; and Proteins; Life Sciences; CD24 Antigen; RNA-Binding Proteins; Cell Biology; Protein Structure, Tertiary; 3. Good health; Hyaluronan Receptors; Neoplastic Stem Cells; Female; RNA Interference; Peptides; Signal Transduction

Although the α6β1 integrin has been implicated in function of breast and other cancer stem cells (CSCs), little is known about its regulation relationship to mechanisms involved genesis CSCs. We report that a CD44high/CD24low population, enriched for CSCs, comprised distinct epithelial mesenchymal populations differ expression two α6 cytoplasmic domain splice variants: α6A α6B. α6Bβ1 defines population necessary CSC function, cannot be executed by integrins. The generation tightly controlled occurs as consequence an autocrine vascular endothelial growth factor (VEGF) signaling culminates transcriptional repression key RNA-splicing factor. These data alter our understanding how contributes cancer, they resolve ambiguities regarding use total (CD49f) biomarker