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Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19450-5. doi: 10.1073/pnas.1309001110. Epub 2013 Nov 11.

Lkb1/Stk11 regulation of mTOR signaling controls the transition of chondrocyte fates and suppresses skeletal tumor formation.

Author information

1
Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-California Institute for Regenerative Medicine Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, CA 90089.

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

PMID:
24218567
PMCID:
PMC3845115
DOI:
10.1073/pnas.1309001110
[Indexed for MEDLINE]
Free PMC Article
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