LKB1, the multitasking tumour suppressor kinase

Journal of Clinical Pathology

Volumn 58, Issue 1, 2005, Pages 15-19

  Marignani, P A ^a  

^a DALHOUSIE UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

GENE PRODUCT; PROTEIN KINASE LKB1; PROTEIN SERINE THREONINE KINASE; WNT PROTEIN;

CANCER INHIBITION; CANCER RISK; CARCINOMA; CELL ACTIVITY; ENZYME ACTIVITY; GENE MUTATION; HETEROZYGOSITY LOSS; HUMAN; MALIGNANT TRANSFORMATION; NONHUMAN; PEUTZ JEGHERS SYNDROME; POLYP; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL POLARITY; CHROMATIN ASSEMBLY AND DISASSEMBLY; DISEASE MODELS, ANIMAL; HUMANS; PEUTZ-JEGHERS SYNDROME; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION;

EID: 11244300732     PISSN: 00219746     EISSN: None     Source Type: Journal    
DOI: 10.1136/jcp.2003.015255     Document Type: Review

References (76)

1. Peutz J. A very remarkable case of familial polyposis of mucous membrane of intestinal tract and accompanied by peculiar pigmentations of skin and mucous membrane [Dutch]. Nederlands Tijdschrift voor Geneeskunde 1921;10:134-46.
2. Jeghers H, McKusick V, Katz K. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits. N Engl J Med 1949;241:992-1005.
3. Hemminki A. The molecular basis and clinical aspects of Peutz-Jeghers syndrome. Cell Mol life Sci 1999;55:735-50.
4. Wirtzfeld DA, Petrelli NJ, Rodriguez-Bigas MA. Hamartomatous polyposis syndromes: molecular genetics, neoplastic risk, and surveillance recommendations. Ann Surg Oncol 2001;8:319-27.
5. Lindor NM, Greene MH. The concise handbook of family cancer syndromes. Mayo familial cancer program. J Natl Cancer Inst 1998;90:1039-71.
6. Giardiello FM, Welsh SB, Hamilton SR, et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 1987;316:1511-14.
7. Karuman P, Gozani O, Odze RD, et al. The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol Cell 2001;7:1307-19.
8. Avizienyte E, Roth S, Loukola A, et al. Somatic mutations in LKB1 are rare in sporadic colorectal and testicular tumors. Cancer Res 1998;58:2087-90.
9. Boardman LA, Couch FJ, Burgart U, et al. Genetic heterogeneity in Peutz-Jeghers syndrome [in process citation]. Hum Mutat 2000;16:23-30.
10. Connolly DC, Katabuchi H, Cliby WA, et al. Somatic mutations in the STK11/ LKB1 gene are uncommon in rare gynecological tumor types associated with Peutz-Jegher's syndrome. Am J Pathol 2000;156:339-45.
11. Hruban RH, Petersen GM, Goggins M, et al. Familial pancreatic cancer. Ann Oncol 1999;10(suppl 4):69-73.
12. Nishioka Y, Kobayashi K, Sagae S, et al. Mutational analysis of STK11 gene in ovarian carcinomas. Jpn J Cancer Res 1999;90:629-32.
13. Shen Z, Wen XF, Lan F, et al. The tumor suppressor gene LKB1 is associated with prognosis in human breast carcinoma. Clin Cancer Res 2002;8:2085-90.
14. Papageorgiou T, Stratakis CA. Ovarian tumors associated with multiple endocrine neoplasias and related syndromes (Carney complex, Peutz-Jeghers syndrome, von Hippel-Lindau disease, Cowden's disease). Int J Gynecol Cancer 2002;12:337-47.
15. Soto N, Rosty C, Jansen M, et al. STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol 2001;159:2017-22.
16. Sonchez-Cespedes M, Parrella P, Esteller M, et al. Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res 2002;62:3659-62.
17. Hemminki A, Tomlinson I, Markie D, et al. Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis [see comments]. Nat Genet 1997;15:87-90.
18. Hemminki A, Markie D, Tomlinson I, et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 1998;391:184-7.
19. Jenne DE, Reimann H, Nezu J, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 1998;18:38-43.
20. Ylikorkala A, Avizienyte E, Tomlinson IP, et al. Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer. Hum Mol Genet 1999;8:45-51.
21. Olschwang S, Boisson C, Thomas G. Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma. J Med Genet 2001;38:356-60.
22. Lim W, Hearle N, Shah B, et al. Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome. Br J Cancer 2003;89:308-13.
23. Scott RJ, Crooks R, Meldrum CJ, et al. Mutation analysis of the STK11/LKB1 gene and clinical characteristics of an Australian series of Peutz-Jeghers syndrome patients. Clin Genet 2002;62:282-7.
24. Le Meur N, Martin C, Saugier-Veber P, et al. Complete germline deletion of the STK11 gene in a family with Peutz-Jeghers syndrome. Eur J Hum Genet 2004;12:415-18.
25. Carretero J, Medina PP, Pio R, et al. Novel and natural knockout lung cancer cell lines for the LKB1/STK11 tumor suppressor gene. Oncogene 2004;23:4037-40.
26. Jimenez AI, Fernandez P, Dominguez O, et al. Growth and molecular profile of lung cancer cells expressing ectopic LKB1: down-regulation of the phospnatidylinositol 3′-phosphate kinase/PTEN pathway. Cancer Res 2003;63:1382-8.
27. Ghaffar H, Sahin F, Sanchez-Cepedes M, et al. LKB1 protein expression in the evolution of glandular neoplasia of the lung. Clin Cancer Res 2003;9:2998-3003.
28. Fernandez P, Carretero J, Medina PP, et al. Distinctive gene expression of human lung adenocarcinomas carrying LKB1 mutations. Oncogene 2004;33:5084-91.
29. Sahin F, Maitra A, Argani P, et al. Loss of Stk11/Lkb1 expression in pancreatic and biliary neoplasms. Mod Pathol 2003;16:686-91.
30. Wang ZJ, Ellis I, Zauber P, et al. Allelic imbalance at the LKB1 (STK11) locus in tumours from patients with Peutz-Jeghers' syndrome provides evidence for a hamartoma-(adenoma)-carcinoma sequence [see comments]. J Pathol 1999;188:9-13.
31. van der Weyden L, Jonkers J, Bradley A. Cancer: stuck at first base. Nature 2002;419:127-8.
32. Tiainen M, Ylikorkala A, Makela TP. Growth suppression by Lkb1 is mediated by a G(1) cell cycle arrest. Proc Natl Acad Sci U S A 1999;96:9248-51.
33. Boudeau J, Kieloch A, Alessi DR, et al. Functional analysis of LKB1/STK11 mutants and two aberrant isoforms found in Peutz-Jeghers syndrome patients. Hum Mutat 2003;21:172.
34. Su JY, Erikson E, Maller JL. Cloning and characterization of a novel serine/ threonine protein kinase expressed in early Xenapus embryos. J Biol Chem 1996;271:14430-7.
35. Smith DP, Spicer J, Smith A, et al. The mouse Peutz-Jeghers syndrome gene Lkb1 encodes a nuclear protein kinase. Hum Mol Genet 1999;8:1479-85.
36. Watts JL, Morton DG, Bestman J, et al. The C. elegans par-4 gene encodes a putative serine-threonine kinase required for establishing embryonic asymmetry. Development 2000;127:1467-75.
37. Martin SG, St Johnston D. A role for Drosophila LKB1 in anterior-posterior axis formation and epithelial polarity. Nature 2003;421:379-84.
38. Nezu J, Oku A, Shimane M. Loss of cytoplasmic retention ability of mutant LKB1 found in Peutz-Jeghers syndrome patients. Biochem Biophys Res Commun 1999;261:750-5.
39. Marignani PA, Kanai F, Carpenter CL. LKB1 associates with Brg1 and is necessary for Brg1-induced growth arrest. J Biol Chem 2001;276:32415-18.
40. Smith DP, Rayrer SI, Niederlander C, et al. LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1. Hum Mol Genef 2001;10:2869-77.
41. Baas AF, Boudeau J, Sapkota GP, et al. Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD. EMBO J 2003;22:3062-72.
42. Boudeau J, Baas AF, Deak M, et al. MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm. EMBO J 2003;22:5102-14.
43. Hawley SA, Boudeau J, Reid JL, et al. Complexes between the LKB1 tumor suppressor, STRADalpha/beta and MO25alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2003;2:28, Epub 2003 Sept 28.
44. Collins SP, Reoma JL, Gamm DM, et al. LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein kinase (PKA) and prenylated in vivo. Biochem J 2000;345:673-80.
45. Sapkota GP, Kieloch A, Lizcana JM, et al. Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90RSK and PKA but not its farnesylation at Cys433 are essential for LKB1 to suppress cell growth. J Biol Chem 2001;276:19469-82.
46. Tiainen M, Vaahtomeri K, Ylikorkala A, et al. Growth arrest by the LKB1 tumor suppressor: induction of p21 (WAF1/CIP1). Hum Mol Genet 2002;11:1497-504.
47. Sapkota GP, Boudeau J, Deak M, et al. Identification and characterization of four novel phosphorylation sites (Ser31, Ser325, Thr336 and Thr366) on LKB1/STK11, the protein kinase mutated in Peutz-Jeghers cancer syndrome. Biochem J 2002;362:481-90.
48. Ossipova O, Bardeesy N, DePinho RA, et al. LKB1 (XEEK1) regulates Wnt signalling in vertebrate development. Nat Cell Biol 2003;14:14.
49. Ylikorkala A, Rossi DJ, Korsisaari N, et al. Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice. Science 2001;293:1323-6.
50. Miyoshi H, Nakau M, Ishikawa TO, et al. Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout mice. Cancer Res 2002;62:2261-6.
51. Fero ML, Rondel E, Gurley KE, et al. The murine gene p27Kip1 is haplo-insufficient for tumour suppression. Nature 1998;396:177-80.
52. Xu X, Brodie SG, Yang X, et al. Haploid loss of the tumor suppressor Smad4/ Dpc4 initiates gastric polyposis and cancer in mice. Oncogene 2000;19:1868-74.
53. Jishage K, Nezu J, Kawase Y, et al. Role of Lkb1, the causative gene of Peutz-Jegher's syndrome, in embryogenesis and polyposis. Proc Natl Acad Sci U S A 2002;99:8903-8.
54. Bardeesy N, Sinha M, Hezel AF, et al. Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 2002;419:162-7.
55. Spicer J, Rayter S, Young N, et al. Regulation of the Wnt signalling component PAR1 A by the Peutz-Jeghers syndrome kinase LKB1. Oncogene 2003;22:4752-6.
56. Baas AF, Kuipers J, van der Wel NN, et al. Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD. Cell 2004;116:457-66.
57. Woods A, Johnstone SR, Dickerson K, et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003;13:2004-8.
58. Lizcano JM, Goransson O, Toth R, et al. LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J 2004;23:833-43.
59. Kwon H, Imbalzano AN, Khavari PA, et al. Nucleosome disruption and enhancement of activator binding by a human SWI/SNF complex [see comments]. Nature 1994;370:477-81.
60. Wang W, Cote J, Xue Y, et al. Purification and biochemical heterogeneity of the mammalian SWI-SNF complex. EMBO J 1990;15:5370-82.
61. Muchardt C, Reves JC, Bourachot B, et al. The hbrm and BRG-1 proteins, components of the human SNF/SWI complex, are phosphorylated and excluded from the condensed chromosomes during mitosis. EMBO J 1996;15:3394-402.
62. Sif S, Stukenberg PT, Kirschner MW, et al. Mitotic inactivation of a human SWI/SNF chromatin remodeling complex. Genes Dev 1998;12:2842-51.
63. Phelan ML, Sif S, Narlikar GJ, et al. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol Cell 1999;3:247-53.
64. Strobeck MW, Knudsen KE, Fribourg AF, et al. BRG-1 is required for RB-mediated cell cycle arrest. Proc Natl Acad Sci U S A 2000;97:7748-53.
65. Shanahan F, Seghezzi W, Parry D, et al. Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest. Mol Cell Biol 1999;19:1460-9.
66. Leberer E, Dignard D, Marcus D, et al. The protein kinase homologue Ste20p is required to link the yeast pheromone response G-protein beta gamma subunits to downstream signalling components. EMBO J 1992;11:4815-24.
67. Thiery JP. Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol 2003;15:740-6.
68. Kemphues KJ, Kusch M, Wolf N. Maternal-effect lethal mutations on linkage group II of Caenorhabditis elegans. Genetics 1988;120:977-86.
69. Brajenovic M, Joberty G, Kuster B, et al. Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. J Biol Chem 2004;279:12804-11.
70. Izumi Y, Hirose T, Tamai Y, et al. An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3. J Cell Biol 1998;143:95-106.
71. Baas AF, Smit L, Clevers H. LKB1 tumor suppressor protein: PARtaker in cell polarity. Trends Cell Biol 2004;14:312-19.
72. Hardie DG, Salt IP, Hawley SA, et al. AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. Biochem J 1999;338:717-22.
73. Hong SP, Leiper FC, Woods A, et al. Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Proc Natl Acad Sci U S A 2003;7:7.
74. Sutherland CM, Hawley SA, McCartney RR, et al. Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex. Curr Biol 2003;13:1299-305.
75. Boudeau J, Sapkota G, Alessi DR. LKB1, a protein kinase regulating cell proliferation and polarity. FEBS Lett 2003;546: 159-65.
76. Kyriakis JM. At the crossroads: AMP-activated kinase and the LKB1 tumor suppressor link cell proliferation to metabolic regulation. J Biol 2003;2:26. Epub 2003 Oct 22.