Lkb1/Stk11 regulation of mTOR signaling controls the transition of chondrocyte fates and suppresses skeletal tumor formation.
Proc Natl Acad Sci U S A, 2013/11/26;110(48):19450-5.
Lai LP[1], Lilley BN, Sanes JR, McMahon AP
Affiliations
PMID: 24218567DOI: 10.1073/pnas.1309001110
Impact factor: 12.779
Abstract
Liver kinase b1 (Lkb1) protein kinase activity regulates cell growth and cell polarity. Here, we show Lkb1 is essential for maintaining a balance between mitotic and postmitotic cell fates in development of the mammalian skeleton. In this process, Lkb1 activity controls the progression of mitotic chondrocytes to a mature, postmitotic hypertrophic fate. Loss of this Lkb1-dependent switch leads to a dramatic expansion of immature chondrocytes and formation of enchondroma-like tumors. Pathway analysis points to a mammalian target of rapamycin complex 1-dependent mechanism that can be partially suppressed by rapamycin treatment. These findings highlight a critical requirement for integration of mammalian target of rapamycin activity into developmental decision-making during mammalian skeletogenesis.
Keywords: cell death; chondrocyte differentiation; endochondral ossification; hypoxia
MeSH terms
AMP-Activated Protein Kinases; Analysis of Variance; Animals; Bromodeoxyuridine; Cell Differentiation; Chondrocytes; Histological Techniques; In Situ Hybridization; Mechanistic Target of Rapamycin Complex 1; Mice; Multiprotein Complexes; Phenylurea Compounds; Protein Serine-Threonine Kinases; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases
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