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

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 48, 2013, Pages 19450-19455

  Lai, Lick Pui ^a,b   Lilley, Brendan N ^b   Sanes, Joshua R ^b   McMahon, Andrew P ^a,b,c  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b HARVARD UNIVERSITY   (United States)

^c HARVARD STEM CELL INSTITUTE   (United States)

Author keywords

Cell death; Chondrocyte differentiation; Endochondral ossification; Hypoxia

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN KINASE LKB1; RAPAMYCIN; VISMODEGIB;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE DEVELOPMENT; BONE TUMOR; CARCINOGENESIS; CARTILAGE CELL; CELL CYCLE PROGRESSION; CELL EXPANSION; CELL FATE; CELL MATURATION; CELL POLARITY; CONTROLLED STUDY; ENCHONDROMA; ENZYME ACTIVITY; ENZYME REGULATION; FEMALE; MALE; MITOSIS; MOUSE; NONHUMAN; PHASE TRANSITION; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; SUPPRESSOR CELL;

CELL DEATH; CHONDROCYTE DIFFERENTIATION; ENDOCHONDRAL OSSIFICATION; HYPOXIA;

ANALYSIS OF VARIANCE; ANIMALS; BROMODEOXYURIDINE; CELL DIFFERENTIATION; CHONDROCYTES; HISTOLOGICAL TECHNIQUES; IN SITU HYBRIDIZATION; MICE; MULTIPROTEIN COMPLEXES; PHENYLUREA COMPOUNDS; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84888350287     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1309001110     Document Type: Article

References (26)

1. Lanske B, et al. (1996) PTH/PTHrP receptor in early development and Indian hedgehog- regulated bone growth. Science 273(5275): 663-666.
2. St-Jacques B, Hammerschmidt M, McMahon AP (1999) Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev 13(16): 2072-2086.
3. Vortkamp A, et al. (1996) Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273(5275): 613-622.
4. Hezel AF, Bardeesy N (2008) LKB1; linking cell structure and tumor suppression. Oncogene 27(55): 6908-6919.
5. Jansen M, Ten Klooster JP, Offerhaus GJ, Clevers H (2009) LKB1 and AMPK family signaling: The intimate link between cell polarity and energy metabolism. Physiol Rev 89(3): 777-798.
6. Ylikorkala A, et al. (2001) Vascular abnormalities and deregulation of VEGF in Lkb1- deficient mice. Science 293(5533): 1323-1326.
7. Hemminki A, et al. (1998) A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391(6663): 184-187.
8. van Lier MG, et al. (2010) High cancer risk in Peutz-Jeghers syndrome: A systematic review and surveillance recommendations. Am J Gastroenterol 105(6): 1258-1264.
9. Udd L, Mäkelä TP (2011) LKB1 signaling in advancing cell differentiation. Fam Cancer 10(3): 425-435.
10. Bardeesy N, et al. (2002) Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 419(6903): 162-167.
11. Ovchinnikov DA, Deng JM, Ogunrinu G, Behringer RR (2000) Col2a1-directed expression of Cre recombinase in differentiating chondrocytes in transgenic mice. Genesis 26(2): 145-146.
12. Tee AR, Blenis J (2005) mTOR, translational control and human disease. Semin Cell Dev Biol 16(1): 29-37.
13. Corradetti MN, Inoki K, Bardeesy N, DePinho RA, Guan KL (2004) Regulation of the TSC pathway by LKB1: Evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev 18(13): 1533-1538.
14. Shaw RJ, et al. (2004) The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 6(1): 91-99.
15. Ho L, et al. (2009) Gli2 and p53 cooperate to regulate IGFBP-3-mediated chondrocyte apoptosis in the progression from benign to malignant cartilage tumors. Cancer Cell 16(2): 126-136.
16. Yang Y, Topol L, Lee H, Wu J (2003) Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development 130(5): 1003-1015.
17. Gable KL, et al. (2006) Diarylureas are small-molecule inhibitors of insulin-like growth factor I receptor signaling and breast cancer cell growth. Mol Cancer Ther 5(4): 1079-1086.
18. Girnita A, et al. (2006) The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells. Clin Cancer Res 12(4): 1383-1391.
19. Huang SM, et al. (2009) Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461(7264): 614-620.
20. Rudin CM, et al. (2009) Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 361(12): 1173-1178.
21. Kronenberg HM (2006) PTHrP and skeletal development. Ann N Y Acad Sci 1068: 1-13.
22. Weir EC, et al. (1996) Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation. Proc Natl Acad Sci USA 93(19): 10240-10245.
23. Levine AJ, Feng Z, Mak TW, You H, Jin S (2006) Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev 20(3): 267-275.
24. Long F, Zhang XM, Karp S, Yang Y, McMahon AP (2001) Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation. Development 128(24): 5099-5108.
25. Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1): 44-57.
26. HuangW, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1): 1-13.