Molecular mechanisms of LKB1 induced cell cycle arrest.

LKB1 is a serine/threonine protein kinase mutated in patients with Peutz-Jeghers syndrome. Biallelic inactivation of LKB1 is present in up to 30% of cases of non-small cell lung cancer (NSCLC). As a tumor suppressor, LKB1 functions in arresting the cell cycle and inhibiting cell growth. LKB1 leads to induction of p21/WAF1 expression in a p53-dependent mechanism, which is mediated by cytoplasmic LKB1 initiating negative regulation of cell growth or nuclear LKB1 directly involved in transcriptional regulation of p21/WAF1. Alternatively, p53 and p21/WAF1-independent mechanism of regulating cell cycle by LKB1 is also reported.