Activation of LKB1-Akt pathway independent of phosphoinositide 3-kinase plays a critical role in the proliferation of hepatocellular carcinoma from nonalcoholic steatohepatitis

Hepatology

Volumn 52, Issue 5, 2010, Pages 1621-1631

  MartíNez LóPez, Nuria ^a   Varela Rey, Marta ^a   FernáNdez Ramos, David ^a   Woodhoo, Ashwin ^a   VáZquez Chantada, Mercedes ^a   Embade, Nieves ^a   Espinosa Hevia, Luis ^a   Bustamante, Francisco Javier ^b   Parada, Luis A ^a   Rodriguez, Manuel S ^a   Lu, Shelly C ^c   Mato, José M ^a   MartíNez Chantar, Maria L ^a  

^a INSTITUTO DE SALUD CARLOS III   (Spain)

^b UNIVERSITY OF THE BASQUE COUNTRY UPV EHU   (Spain)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HERPESVIRUS ASSOCIATED UBIQUITIN SPECIFIC PROTEASE; HU ANTIGEN; HU ANTIGEN R; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; METHIONINE ADENOSYLTRANSFERASE; METHIONINE ADENOSYLTRANSFERASE 1A; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN KINASE LKB1; PROTEIN P53; PROTEINASE; S ADENOSYLMETHIONINE; UNCLASSIFIED DRUG;

ALCOHOLIC FATTY LIVER; ANIMAL CELL; APOPTOSIS; ARTICLE; CARCINOGENESIS; CELL ISOLATION; CELL SURVIVAL; CONTROLLED STUDY; CYTOPLASM; HERPES VIRUS; HUMAN; HUMAN CELL; HUMAN TISSUE; KNOCKOUT MOUSE; LIVER BIOPSY; LIVER CELL CARCINOMA; MALE; MALIGNANT TRANSFORMATION; MOUSE; NONALCOHOLIC FATTY LIVER; NONHUMAN; NUCLEOCYTOPLASMIC TRANSPORT; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; STAINING; TUMOR DIFFERENTIATION;

EID: 78049497993     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.23860     Document Type: Article

References (40)

1. Varela-Rey M, Embade N, Ariz U, Lu SC, Mato JM, Martínez-Chantar ML. Non-alcoholic steatohepatitis and animal models: understanding the human disease. Int J Biochem Cell Biol 2009; 41: 969-976.
2. Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 2002; 31: 339-346.
3. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature 2000; 408: 307-310.
4. Yahagi N, Shimano H, Matsuzaka T, Sekiya M, Najima Y, Okazaki S, et al. p53 involvement in the pathogenesis of fatty liver disease. J Biol Chem 2004; 279: 20571-20575.
5. Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, et al. Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet 1998; 63: 1641-1650.
6. Zhong D, Liu X, Khuri FR, Sun SY, Vertino PM, Zhou W. LKB1 is necessary for Akt-mediated phosphorylation of proapoptotic proteins. Cancer Res 2008; 68: 7270-7277.
7. Zeng PY, Berger SL. LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate transcriptional activation. Cancer Res 2006; 66: 10701-10708.
8. Vázquez-Chantada M, Ariz U, Varela-Rey M, Embade N, Martínez-Lopez N, Fernández-Ramos D, et al. Evidence for LKB1/AMP-activated protein kinase/ endothelial nitric oxide synthase cascade regulated by hepatocyte growth factor, S-adenosylmethionine, and nitric oxide in hepatocyte proliferation. HEPATOLOGY 2009; 49: 608-617.
9. Martínez-Chantar ML, Vázquez-Chantada M, Garnacho M, Latasa MU, Varela-Rey M, Dotor J, et al. S-adenosylmethionine regulates cytoplasmic HuR via AMP-activated kinase. Gastroenterology 2006; 131: 223-232.
10. Mato JM, Lu SC. Role of S-adenosyl-L-methionine in liver health and injury. HEPATOLOGY 2007; 45: 1306-1312.
11. Mato JM, Martinez-Chantar ML, Lu SC. Methionine metabolism and liver disease. Annu Rev Nutr 2008; 28: 273-293.
12. Lu SC, Alvarez L, Huang ZZ, Chen L, An W, Corrales FJ, et al. Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Proc Natl Acad Sci USA 2001; 98: 5560-5565.
13. Martínez-Chantar ML, Corrales FJ, Martínez-Cruz LA, García-Trevijano ER, Huang ZZ, Chen L, et al. Spontaneous oxidative stress and liver tumors in mice lacking methionine adenosyltransferase 1A. FASEB J 2002; 16: 1292-1294.
14. Morikawa K, Walker SM, Nakajima M, Pathak S, Jessup JM, Fidler IJ. Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res 1988; 48: 6863-6871.
15. Leffert HL, Koch KS, Moran T, Williams M. Liver cells. Methods Enzymol 1979; 58: 536-544.
16. Vázquez-Chantada M, Fernández-Ramos D, Embade N, Martínez-Lopez N, Varela-Rey M, Woodhoo A, et al. HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation and carcinogenesis. 2010; 138: 1943-1953.
17. Von Mikecz A, Chen M, Rockel T, Scharf A. The nuclear ubiquitin-proteasome system: visualization of proteasomes, protein aggregates, and proteolysis in the cell nucleus. Methods Mol Biol 2008; 463: 191-202.
18. Moll UM, Riou G, Levine AJ. Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proc Natl Acad Sci USA 1992; 89: 7262-7266.
19. Moll UM, LaQuaglia M, Benárd J, Riou G. Wild-type p53 protein undergoes cytoplasmic sequestration in undifferentiated neuroblastomas but not in differentiated tumors. Proc Natl Acad Sci USA 1995; 92: 4407-4411.
20. Bosari S, Viale G, Bossi P, Maggioni M, Coggi G, Murray JJ, et al. Cytoplasmic accumulation of p53 protein: an independent prognostic indicator in colorectal adenocarcinomas. J Natl Cancer Inst 1994; 86: 681-687.
21. Brennan CM, Steitz JA. HuR and mRNA stability. Cell Mol Life Sci 2001; 58: 266-277.
22. Alarcon-Vargas D, Ronai Z. p53-Mdm2-the affair that never ends. Carcinogenesis 2002; 23: 541-547.
23. Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev 1999; 13: 2905-2927.
24. Romashkova JA, Makarov SS. NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 1999; 401: 86-90.
25. Yang Z, Yi J, Li X, Long W. Correlation between loss of PTEN expression and PKB/AKT phosphorylation in hepatocellular carcinoma. J Huazhong Univ Sci Technolog Med Sci 2005; 25: 45-47.
26. Bhaskar PT, Hay N. The two TORCs and Akt. Dev Cell 2007; 12: 487-502.
27. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307: 1098-1101.
28. Kristof AS, Marks-Konczalik J, Billings E, Moss J. Stimulation of signal transducer and activator of transcription-1 (STAT1)-dependent gene transcription by lipopolysaccharide and interferon-gamma is regulated by mammalian target of rapamycin. J Biol Chem 2003; 278: 33637-33644.
29. Huang C, Li J, Ke Q, Leonard SS, Jiang BH, Zhong XS, et al. Ultraviolet-induced phosphorylation of p70(S6K) at Thr(389) and Thr(421)/Ser(424) involves hydrogen peroxide and mammalian target of rapamycin but not Akt and atypical protein kinase C. Cancer Res 2002; 62: 5689-5697.
30. Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, et al. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signalling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell 2006; 11: 859-871.
31. Levine YC, Li GK, Michel T. Agonist-modulated regulation of AMP-activated protein kinase (AMPK) in endothelial cells. Evidence for an AMPK -> Rac1 -> Akt -> endothelial nitric-oxide synthase pathway. J Biol Chem 2007; 282: 20351-20364.
32. González-Rodriguez A, Alba J, Zimmerman V, Kozma SC, Valverde AM. S6K1 deficiency protects against apoptosis in hepatocytes. HEPATOLOGY 2009: 50: 216-229.
33. Ogawara Y, Kishishita S, Obata T, Isazawa Y, Suzuki T, Tanaka K, et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem 2002; 277: 21843-21850.
34. Stevenson LF, Sparks A, Allende-Vega N, Xirodimas DP, Lane DP, Saville MK. The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2. EMBO J 2007; 26: 976-986.
35. Fernández-Montalván A, Bouwmeester T, Joberty G, Mader R, Mahnke M, Pierrat B, et al. Biochemical characterization of USP7 reveals post-translational modification sites and structural requirements for substrate processing and subcellular localization. FEBS J 2007; 274: 4256-4270.
36. Westmark CJ, Bartleson VB, Malter JS. RhoB mRNA is stabilized by HuR after UV light. Oncogene 2005; 24: 502-511.
37. Wang W, Caldwell MC, Lin S, Furneaux H, Gorospe M. HuR regulates cyclin A and cyclin B1 mRNA stability during cell proliferation. EMBO J 2000; 19: 2340-2350.
38. Lopez de Silanes I, Lal A, Gorospe M. HuR: post-transcriptional paths to malignancy. RNA Biol 2005; 2: 11-13.
39. Ullrich SJ, Sakaguchi K, Lees-Miller SP, Fiscella M, Mercer WE, Anderson CW, et al. Phosphorylation at Ser-15 and Ser-392 in mutant p53 molecules from human tumors is altered compared to wild-type p53. Proc Natl Acad Sci USA 1993; 90: 5954-5958.
40. Becker K, Marchenko ND, Maurice M, Moll UM. Hyperubiquitylation of wild-type p53 contributes to cytoplasmic sequestration in neuroblastoma. Cell Death Differ 2007; 14: 1350-1360.