| First Author | Iglesias-Bartolome R | Year | 2015 |
| Journal | Nat Cell Biol | Volume | 17 |
| Issue | 6 | Pages | 793-803 |
| PubMed ID | 25961504 | Mgi Jnum | J:301078 |
| Mgi Id | MGI:6204056 | Doi | 10.1038/ncb3164 |
| Citation | Iglesias-Bartolome R, et al. (2015) Inactivation of a Galpha(s)-PKA tumour suppressor pathway in skin stem cells initiates basal-cell carcinogenesis. Nat Cell Biol 17(6):793-803 |
| abstractText | Genomic alterations in GNAS, the gene coding for the Galphas heterotrimeric G protein, are associated with a large number of human diseases. Here, we explored the role of Galphas on stem cell fate decisions by using the mouse epidermis as a model system. Conditional epidermal deletion of Gnas or repression of PKA signalling caused a remarkable expansion of the stem cell compartment, resulting in rapid basal-cell carcinoma formation. In contrast, inducible expression of active Galphas in the epidermis caused hair follicle stem cell exhaustion and hair loss. Mechanistically, we found that Galphas-PKA disruption promotes the cell autonomous Sonic Hedgehog pathway stimulation and Hippo signalling inhibition, resulting in the non-canonical activation of GLI and YAP1. Our study highlights an important tumour suppressive function of Galphas-PKA, limiting the proliferation of epithelial stem cells and maintaining proper hair follicle homeostasis. These findings could have broad implications in multiple pathophysiological conditions, including cancer. |
