First Author | Rutherford TR | Year | 2021 |
Journal | Cell Death Dis | Volume | 12 |
Issue | 10 | Pages | 872 |
PubMed ID | 34561423 | Mgi Jnum | J:337116 |
Mgi Id | MGI:6784461 | Doi | 10.1038/s41419-021-04133-5 |
Citation | Rutherford TR, et al. (2021) Anoikis resistance in mammary epithelial cells is mediated by semaphorin 7a. Cell Death Dis 12(10):872 |
abstractText | Semaphorin-7a (SEMA7A), best known as a neuroimmune molecule, plays a diverse role in many cellular processes and pathologies. Here, we show that SEMA7A promotes anoikis resistance in cultured mammary epithelial cells through integrins and activation of pro-survival kinase AKT, which led us to investigate a role for SEMA7A during postpartum mammary gland involution-a normal developmental process where cells die by anoikis. Our results reveal that SEMA7A is expressed on live mammary epithelial cells during involution, that SEMA7A expression is primarily observed in alpha6-integrin expressing cells, and that luminal progenitor cells, specifically, are decreased in mammary glands of SEMA7A-/- mice during involution. We further identify a SEMA7A-alpha6/beta1-integrin dependent mechanism of mammosphere formation and chemoresistance in mammary epithelial cells and suggest that this mechanism is relevant for recurrence in breast cancer patients. |