| First Author | Byekova YA | Year | 2011 |
| Journal | Arch Biochem Biophys | Volume | 508 |
| Issue | 2 | Pages | 204-11 |
| PubMed ID | 21272562 | Mgi Jnum | J:171639 |
| Mgi Id | MGI:4950657 | Doi | 10.1016/j.abb.2011.01.006 |
| Citation | Byekova YA, et al. (2011) Liver kinase B1 (LKB1) in the pathogenesis of UVB-induced murine basal cell carcinoma. Arch Biochem Biophys 508(2):204-11 |
| abstractText | LKB1, a known tumor suppressor, is mutated in Peutz-Jeghers Syndrome (PJS). It is responsible for the enhanced cancer risk in patients with PJS. Dysregulation of LKB1-dependent signaling also occurs in various epithelial cancers. UVB alters the expression of LKB1, though its role in the pathogenesis of skin cancer is unknown. Here we describe upregulation of LKB1 expression in UVB-induced murine basal cell carcinoma (BCC) and in human skin tumor keratinocytes. AMP-kinase and acetyl Co-A carboxylase, the downstream LKB1 targets, are also enhanced in this neoplasm. In addition, p-Akt, a kinase which inactivates GSK3beta by its phosphorylation, is enhanced in BCCs. Consistently, an accumulation of p-GSK3beta and an increase in activated nuclear beta-catenin are found. mTOR signaling, which is also inhibited by LKB1, remains upregulated in BCCs. However, a marked decrease in the expression of sestrins, which function as potent negative regulators of mTOR is observed. Metformin, a known chemical inducer of this pathway, was found effective in immortalized HaCaT keratinocytes, but failed to activate the LKB1-dependent signaling in human carcinoma A431 cells. Thus, our data show that the LKB1/AMPK axis fails to regulate mTOR pathway, and a complex regulatory mechanism exists for the persistent mTOR activation in murine BCCs. |
