A role for LKB1 gene in human cancer beyond the Peutz–Jeghers syndrome

Phosphorylation of Serine 399 in LKB1 Protein Short Form by Protein Kinase Cζ Is Required for Its Nucleocytoplasmic Transport and Consequent AMP-activated Protein Kinase (AMPK) Activation

“…Liver kinase B1 (LKB1) is a tumor suppressor gene whose inactivating mutations are implicated in various sporadic cancers and are responsible for the majority of Peutz-Jeghers syndrome cases (1)(2)(3)(4)(5). Expression of LKB1 is ubiquitous in many cell types and tissues, and its high expression in fetal tissues is consistent with the critical role of LKB1 in embryonic development (6 -9).…”

Role of LKB1 in lung cancer development

“…Table 1 reviews a sample of the largest of these reports in the area of lung cancer, and includes associated epigenetic findings. Although infrequently mutated in spontaneous tumours, LKB1 point mutations were seen in a pattern mirroring those seen in association with PJS, including cervix, gastrointestinal, and pancreas (Avizienyte et al, 1999;Sanchez-Cespedes, 2007). A range of atypical PJS tumours was also identified, including prostate and melanoma.…”

Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer

“…As the biology of LKB1 is complex and linked with many signaling pathways spanning cell polarity, cellular metabolism and cell cycle control (Katajisto et al, 2007;Sanchez-Cespedes, 2007;Shah et al, 2008), there remains an imperfect understanding of how somatic or Enhanced activity of the CREB co-activator Crtc1 T Komiya et al inherited mutations of LKB1 lead to tumorigenesis. We have now identified another element to this pathway by observing that somatic loss of LKB1 in tumor cell lines is associated with enhanced Crtc1 activation resulting in deregulated expression of several cAMP/ CREB-inducible targets, including NR4A2/Nurr1.…”