LKB1 signaling in advancing cell differentiation

The Peutz-Jeghers syndrome (PJS) culprit kinase LKB1 phosphorylates and activates multiple intracellular kinases regulating cell metabolism and polarity. The relevance of each of these pathways is highly variable depending on the tissue type, but typically represents functions of differentiated cells. These include formation and maintenance of specialized cell compartments in nerve axons, swift refunneling of metabolites and restructuring of cell architecture in response to environmental cues in committed lymphocytes, and ensuring energy-efficient oxygen-based energy expenditure. Such features are often lost or reduced in cancer cells, and indeed LKB1 defects in PJS-associated and sporadic cancers and even the benign PJS polyps lead to differentiation defects, including expansion of partially differentiated epithelial cells in PJS polyps and epithelial-to-mesenchymal transition in carcinomas. This review focuses on the involvement of LKB1 in the differentiation of epithelial, mesenchymal, hematopoietic and germinal lineages.