LKB1/AMPK/mTOR Signaling Pathway in Non-small-cell Lung Cancer

Asian Pacific Journal of Cancer Prevention

Volumn 14, Issue 7, 2013, Pages 4033-4039

  Han, Dong ^a   Li, Shao Jun ^a   Zhu, Yan Ting ^a   Liu, Lu ^a   Li, Man Xiang ^a  

^a XI'AN JIAOTONG UNIVERSITY   (China)

Author keywords

AMPK; LKB1; MTOR; NSCLC; Therapeutic target

Indexed keywords

AMP ACTIVATED PROTEIN KINASE KINASE; AMP-ACTIVATED PROTEIN KINASE KINASE; ANTINEOPLASTIC AGENT; MTOR PROTEIN, HUMAN; PROTEIN KINASE; PROTEIN SERINE THREONINE KINASE; STK11 PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; HUMAN; LUNG NON SMALL CELL CANCER; LUNG TUMOR; METABOLISM; MOLECULARLY TARGETED THERAPY; SHORT SURVEY; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; HUMANS; LUNG NEOPLASMS; MOLECULAR TARGETED THERAPY; PROTEIN KINASES; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84885456615     PISSN: 15137368     EISSN: 2476762X     Source Type: Journal    
DOI: 10.7314/APJCP.2013.14.7.4033     Document Type: Short Survey

References (58)

1. Chapuis N, Tamburini J, Green AS, et al (2010). Perspectives on inhibiting mTOR as a future treatment strategy for hematological malignancies. Leukemia, 24, 1686-99.
2. Choo AY, Yoon SO, Kim SG, Roux PP, Blenis J (2008). Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proc Natl Acad Sci U S A, 105, 17414-9.
3. Don AS, Hogg PJ (2004). Mitochondria as cancer drug targets. Trends Mol Med, 10, 372-8.
4. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD (2005). Metformin and reduced risk of cancer in diabetic patients. BMJ, 330, 1304-5.
5. Feldman ME, Apsel B, Uotila A, et al (2009). Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol, 7, e38.
6. Guertin DA, Sabatini DM (2007). Defining the role of mTOR in cancer. Cancer Cell, 12, 9-22.
7. Guertin DA, Stevens DM, Saitoh M, et al (2009). mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice. Cancer Cell, 15, 148-59.
8. Gwinn DM, Shackelford DB, Egan DF, et al (2008). AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell, 30, 214-26.
9. Hahn-Windgassen A, Nogueira V, Chen CC, et al (2005). Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. J Biol Chem, 280, 32081-9.
10. Han S, Khuri FR, Roman J (2006). Fibronectin stimulates non-small cell lung carcinoma cell growth through activation of Akt/mammalian target of rapamycin/S6 kinase and inactivation of LKB1/AMP-activated protein kinase signal pathways. Cancer Res, 66, 315-23.
11. Han S, Roman J (2006). Rosiglitazone suppresses human lung carcinoma cell growth through PPARgamma-dependent and PPARgamma-independent signal pathways. Mol Cancer Ther, 5, 430-7.
12. Hardie DG (2007). AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol, 8, 774-85.
13. Hardie DG (2011). AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev, 25, 1895-908.
14. Hawley SA, Boudeau J, Reid JL, et al (2003). Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol, 2, 28.
15. Hemminki A, Markie D, Tomlinson I, et al (1998). A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature, 391, 184-7.
16. Holz MK, Ballif BA, Gygi SP, Blenis J (2005). mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell, 123, 569-80.
17. Horman S, Vertommen D, Heath R, et al (2006). Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser485/491. J Biol Chem, 281, 5335-40.
18. Huang J, Manning BD (2008). The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J, 412, 179-90.
19. Huang X, Wullschleger S, Shpiro N, et al (2008). Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J, 412, 211-21.
20. Hwang SK, Piao L, Lim HT, et al (2010). Suppression of lung tumorigenesis by leucine zipper/EF hand-containing transmembrane-1. PLoS One, 5.
21. Inoki K, Zhu T, Guan KL (2003). TSC2 mediates cellular energy response to control cell growth and survival. Cell, 115, 577-90.
22. Jacinto E, Loewith R, Schmidt A, et al (2004). Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol, 6, 1122-8.
23. Jemal A, Bray F, Center M, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
24. Jemal A, Siegel R, Xu J, Ward E (2010). Cancer statistics, 2010. CA Cancer J Clin, 60, 277-300.
25. Jenne DE, Reimann H, Nezu J, et al (1998). Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet, 18, 38-43.
26. Ji H, Ramsey MR, Hayes DN, et al (2007). LKB1 modulates lung cancer differentiation and metastasis. Nature, 448, 807-10.
27. Jin HO, Hong SE, Woo SH, et al (2012). Silencing of Twist1 sensitizes NSCLC cells to cisplatin via AMPK-activated mTOR inhibition. Cell Death Dis, 3, e319.
28. Jin Q, Feng L, Behrens C, et al (2007). Implication of AMP-activated protein kinase and Akt-regulated survivin in lung cancer chemopreventive activities of deguelin. Cancer Res, 67, 11630-9.
29. Jones RG, Plas DR, Kubek S, et al (2005). AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell, 18, 283-93.
30. Khan N, Afaq F, Khusro FH, et al (2012). Dual inhibition of phosphatidylinositol 3-kinase/Akt and mammalian target of rapamycin signaling in human nonsmall cell lung cancer cells by a dietary flavonoid fisetin. Int J Cancer, 130, 1695-705.
31. Lee SO, Abdelrahim M, Yoon K, et al (2010). Inactivation of the orphan nuclear receptor TR3/Nur77 inhibits pancreatic cancer cell and tumor growth. Cancer Res, 70, 6824-36.
32. Lee SO, Andey T, Jin UH, et al (2012). The nuclear receptor TR3 regulates mTORC1 signaling in lung cancer cells expressing wild-type p53. Oncogene, 31, 3265-76.
33. Liu L, Cash TP, Jones RG, et al (2006). Hypoxia-induced energy stress regulates mRNA translation and cell growth. Mol Cell, 21, 521-31.
34. Mankouri J, Tedbury PR, Gretton S, et al (2010). Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase. Proc Natl Acad Sci U S A, 107, 11549-54.
35. Matsumoto S, Iwakawa R, Takahashi K, et al (2007). Prevalence and specificity of LKB1 genetic alterations in lung cancers. Oncogene, 26, 5911-8.
36. Memmott RM, Gills JJ, Hollingshead M, et al (2008). Phosphatidylinositol ether lipid analogues induce AMP-activated protein kinase-dependent death in LKB1-mutant non small cell lung cancer cells. Cancer Res, 68, 580-8.
37. Nanjundan M, Byers LA, Carey MS, et al (2010). Proteomic profiling identifies pathways dysregulated in non-small cell lung cancer and an inverse association of AMPK and adhesion pathways with recurrence. J Thorac Oncol, 5, 1894-904.
38. Rauch A, Schellmoser S, Kraus C, et al (2001). First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation. Am J Med Genet, 99, 338-42.
39. Rothbart SB, Racanelli AC, Moran RG (2010). Pemetrexed indirectly activates the metabolic kinase AMPK in human carcinomas. Cancer Res, 70, 10299-309.
40. Sanchez-Cespedes M, Parrella P, Esteller M, et al (2002). Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res, 62, 3659-62.
41. Sanli T, Liu C, Rashid A, et al (2011). Lovastatin sensitizes lung cancer cells to ionizing radiation: modulation of molecular pathways of radioresistance and tumor suppression. J Thorac Oncol, 6, 439-50.
42. Sanli T, Rashid A, Liu C, et al (2010). Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells. Int J Radiat Oncol Biol Phys, 78, 221-9.
43. Shackelford DB, Shaw RJ (2009). The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer, 9, 563-75.
44. Shackelford DB, Vasquez DS, Corbeil J, et al (2009). mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome. Proc Natl Acad Sci U S A, 106, 11137-42.
45. Shao JJ, Zhang AP, Qin W, et al (2012). AMP-activated protein kinase (AMPK) activation is involved in chrysin-induced growth inhibition and apoptosis in cultured A549 lung cancer cells. Biochem Biophys Res Commun, 423, 448-53.
46. Shaw RJ, Bardeesy N, Manning BD, et al (2004). The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell, 6, 91-9.
47. Shaw RJ, Cantley LC (2006). Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature, 441, 424-30.
48. Storozhuk Y, Sanli T, Hopmans SN, et al (2012). Chronic modulation of AMP-Kinase, Akt and mTOR pathways by ionizing radiation in human lung cancer xenografts. Radiat Oncol, 7, 71.
49. Street A, Macdonald A, Crowder K, Harris M (2004). The Hepatitis C virus NS5A protein activates a phosphoinositide 3-kinase-dependent survival signaling cascade. J Biol Chem, 279, 12232-41.
50. Tamm I, Wang Y, Sausville E, et al (1998). IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res, 58, 5315-20.
51. Vaira V, Lee CW, Goel HL, et al (2007). Regulation of survivin expression by IGF-1/mTOR signaling. Oncogene, 26, 2678-84.
52. Wang HW, Lin CP, Chiu JH, et al (2007). Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin. Int J Cancer, 120, 2019-27.
53. Wang X, Ling MT, Guan XY, et al (2004). Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells. Oncogene, 23, 474-82.
54. William WN, Kim JS, Liu DD, et al (2012). The impact of phosphorylated AMP-activated protein kinase expression on lung cancer survival. Ann Oncol, 23, 78-85.
55. Woods A, Johnstone SR, Dickerson K, et al (2003). LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol, 13, 2004-8.
56. Wullschleger S, Loewith R, Hall MN (2006). TOR signaling in growth and metabolism. Cell, 124, 471-84.
57. Zhang XK (2007). Targeting Nur77 translocation. Expert Opin Ther Targets, 11, 69-79.
58. Zheng B, Jeong JH, Asara JM, et al (2009). Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation. Mol Cell, 33, 237-47.