NUAK2: An emerging acral melanoma oncogene

Oncotarget

Volumn 2, Issue 9, 2011, Pages 695-704

  Namiki, Takeshi ^a,b   Coelho, Sergio G ^a   Hearing, Vincent J ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b YOKOHAMA CITY MINATO RED CROSS HOSPITAL   (Japan)

Author keywords

Acral melanoma; Metastasis; Migration; NUAK2; Oncogene

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; PROTEIN NUAK2; UNCLASSIFIED DRUG; NUAK2 PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE;

ACRAL MELANOMA; ARTICLE; CANCER SURVIVAL; CARCINOGENESIS; CELL MIGRATION; CELL PROLIFERATION; CHROMOSOME ABERRATION; COMPARATIVE GENOMIC HYBRIDIZATION; ENZYME ACTIVITY; GENE MUTATION; GENETIC DISORDER; HUMAN; MELANOMA; MELANOMA CELL; NONHUMAN; NUAK2 GENE; ONCOGENE; REGULATORY MECHANISM; ANIMAL; CELL TRANSFORMATION; GENETICS; PATHOLOGY; REVIEW; SKIN TUMOR;

ANIMALS; CELL TRANSFORMATION, NEOPLASTIC; HUMANS; MELANOMA; ONCOGENES; PROTEIN-SERINE-THREONINE KINASES; SKIN NEOPLASMS;

EID: 84857956747     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.325     Document Type: Article

References (98)

1. Haber DA, Gray NS, Baselga J. The evolving war on cancer. Cell. 2011; 145: 19-24.
2. Sidransky D. Emerging molecular markers of cancer. Nat Rev Cancer. 2002; 2: 210-19.
3. Hunter T. Treatment for chronic myelogenous leukemia: the long road to imatinib. J Clin Invest. 2007; 117: 2036-43.
4. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teaque J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002; 417: 949-54.
5. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010; 363: 809-19.
6. Solit DB, Rosen N. Resistance to BRAF inhibition in melanomas. N Engl J Med. 2011; 364: 772-74.
7. Edmunds SC, Cree IA, Di Nicolantonio F, Hungerford JL, Hurren JS, Kelsell DP. Absence of BRAF gene mutations in uveal melanomas in contrast to cutaneous melanomas. Br J Cancer. 2003; 88: 1403-5.
8. Maldonado JL, Fridlyand J, Patel H, Jain AN, Busam K, Kageshita T, Ono T, Albertson DG, Pinkel D, Bastian BC. Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst. 2003; 95: 1878-90.
9. Edwards RH, Ward MR, Wu H, Medina CA, Brose MS, Volpe P, Nussen-Lee S, Haupt HM, Martin AM, Herlyn M, Lessin SR, Weber BL. Absence of BRAF mutations in UV-protected mucosal melanomas. J Med Genet. 2004; 41: 270-2.
10. Sasaki Y, Niu C, Makino R, Kudo C, Sun C, Watanabe H, Matsunaga J, Takahashi K, Tagami H, Aiba S, Horii A. BRAF point mutations in primary melanoma show different prevalences by subtype. J Invest Dermatol. 2004; 123: 177-83.
11. Helmke BM, Mollenhauer J, Herold-Mende C, Benner A, Thome M, Gassler N, Wahl W, Lyer S, Poustka A, Otto HF, Deichmann M. BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular level. Gastroenterology. 2004; 127: 1815-20.
12. Landi MT, Bauer J, Pfeiffer RM, Elder DE, Hulley B, Minghetti P, Calista D, Kanetsky PA, Pinkel D, Bastian BC. MC1R germline variants confer risk for BRAF-mutant melanoma. Science. 2006; 313: 521-22.
13. Bastian BC, LeBoit PE, Hamm H, Bröcker EB, Pinkel D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 1998; 58: 2170-75.
14. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006; 24: 4340-46.
15. Beadling C, Jacobson-Dunlop E, Hodi FS, Le C, Warrick A, Patterson J, Town A, Harlow A, Cruz F 3rd, Azar S, Rubin BP, Muller S, West R, Heinrich MC, Corless CL. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res. 2008; 14: 6821-28.
16. Namiki T, Tanemura A, Valencia JC, Coelho SG, Passeron T, Kawaguchi M, Vieira WD, Ishikawa M, Nishijima W, Izumo T, Kaneko Y, Katayama I, Yamaguchi Y, Yin L, Polley EC, Liu H and et al. AMP kinase-related kinase NUAK2 affects tumor growth, migration, and clinical outcome of human melanoma. Proc Natl Acad Sci USA. 2011; 108: 6597-602.
17. Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol. 2007; 8: 774-785.
18. Kato K, Ogura T, Kishimoto A, Minegishi Y, Nakajima N, Miyazaki M, Esumi H. Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation. Oncogene. 2002; 21: 6082-90.
19. Carling D, Aguan K, Woods A, Verhoeven AJ, Beri RK, Brennan CH, Sidebottom C, Davison MD, Scott J. Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism. J Biol Chem. 1994; 269: 11442-8.
20. Mitchelhill KI, Stapleton D, Gao G, House C, Michell B, Katsis F, Witters LA, Kemp BE. Mammalian AMPactivated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase. J Biol Chem. 1994; 269: 2361-4.
21. Stapleton D, Mitchelhill KI, Gao G, Widmer J, Michell BJ, Teh T, House CM, Fernandez CS, Cox T, Witters LA, Kemp BE. Mammalian AMP-activated protein kinase subfamily. J Biol Chem. 1996; 271: 611-4.
22. Heyer BS, Warsowe J, Solter D, Knowles BB, Ackerman SL. New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo. Mol Reprod Dev. 1997; 47: 148-56.
23. Lefebvre DL, Bai Y, Shahmolky N, Sharma M, Poon R, Drucker DJ, Rosen CF. Identification and characterization of a novel sucrose-non-fermenting protein kinase/AMPactivated protein kinase-related protein kinase, SNARK. Biochem J. 2001; 355: 297-305.
24. Suzuki A, Kusakai G, Kishimoto A, Minegichi Y, Ogura T, Esumi H. Induction of cell-cell detachment during glucose starvation through F-actin conversion by SNARK, the fourth member of the AMP-activated protein kinase catalytic subunit family. Biochem Biophys Res Commun. 2003; 311: 156-61.
25. Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Lavin MF, Esumi H. Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein. J Biol Chem. 2003; 278: 48-53.
26. Lizcano JM, Göransson O, Toth R, Deak M, Morrice NA, Boudeau J, Hawley SA, Udd L, Mäkelä TP, Hardie DG, Alessi DR. LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 2004; 23: 833-43
27. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002; 298: 1912-34.
28. Woodard J, Platanias LC. AMP-activated kinase (AMPK)-generated signals in malignant melanoma cell growth and survival. Biochem Biophys Res Commun. 2010; 398: 135-9.
29. Kusakai G, Suzuki A, Ogura T, Miyamoto S, Ochiai A, Kaminishi M, Esumi H. ARK5 expression in colorectal cancer and its implications for tumor progression. Am J Pathol. 2004; 164: 987-95.
30. Luo Z, Zang M, Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol. 2010; 6: 457-70.
31. Vazquez-Martin A, Oliveras-Ferraros C, Lopez-Bonet E, Menendez JA. AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor. Cell Cycle. 2009; 8: 3679-83.
32. Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. 2009; 9: 563-75.
33. Suzuki A, Lu J, Kusakai G, Kishimoto A, Ogura T, Esumi H. ARK5 is a tumor invasion-associated factor downstream of Akt signaling. Mol Cell Biol. 2004; 24: 3526-35.
34. Tsuchihara K, Ogura T, Fujioka R, Fujii S, Kuga W, Saito M, Ochiya T, Ochiai A, Esumi H. Susceptibility of Snark-deficient mice to azoxymethane-induced colorectal tumorigenesis and the formation of aberrant crypt foci. Cancer Sci. 2008; 99: 677-82.
35. Becher R, Gibas Z, Karakousis C, Sandberg AA. Nonrandom chromosome changes in malignant melanoma. Cancer Res. 1983; 43: 5010-16.
36. Trent JM, Rosenfeld SB, Meyskens FL. Chromosome 6q involvement in human malignant melanoma. Cancer Genet Cytogenet. 1983; 9: 177-80.
37. Balaban G, Herlyn M, Guerry D 4th, Bartolo R, Koprowski H, Clark WH, Nowell PC. Cytogenetics of human malignant melanoma and premalignant lesions. Cancer Genet Cytogenet. 1984; 11: 429-39.
38. Parmiter AH, Balaban G, Herlyn M, Clark WH, Nowell PC. A t(1;19) chromosome translocation in three cases of human malignant melanoma. Cancer Res. 1986; 46: 1526-29.
39. Cowan JM, Halaban R, Lane AT, Francke U. The involvement of 6p in melanoma. Cancer Genet Cytogenet. 1986; 20: 255-61.
40. Nowell PC, Hungerford DA. A minute chromosome in human chronic granulocytic leukemia. Science. 1960; 132: 1497.
41. Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973; 243: 290-93.
42. de Klein A, van Kessel AG, Grosveld G, Bartram CR, Haqemeijer A, Bootsma D, Spurr NK, Heisterkamp N, Groffen J, Stephenson JR. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukemia. Nature. 1982; 300: 765-67.
43. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell. 1984; 36: 93-9.
44. Shtivelman E, Lifshitz B, Gale RP, Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukemia. Nature. 1985; 315: 550-54.
45. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996; 2: 561-66.
46. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001; 344: 1038-42.
47. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001; 344: 1031-37.
48. Koretzky GA. The legacy of the Philadelphia chromosome. J Clin Invest. 2007; 117: 2030-32.
49. Thompson FH, Emerson J, Olson S, Weinstein R, Leavitt SA, Leong SP, Emerson S, Trent JM, Nelson MA, Salmon SE, Taetle R. Cytogenetics of 158 patients with regional or disseminated melanoma. Subset analysis of near-diploid and simple karyotypes. Cancer Genet Cytogenet. 1995; 83: 93-104.
50. Trent JM, Thompson FH, Meyskens FL. Identification of a recurring translocation site involving chromosome 6 in human malignant melanoma. Cancer Res. 1989; 49: 420-23.
51. Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992; 258: 818-21.
52. Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D, Collins C, Kuo WL, Chen C, Zhai Y, Dairkee SH, Ljung BM, Gray JW, Albertson DG. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet. 1998; 20: 207-11.
53. Bastian BC, Olshen AB, LeBoit PE, Pinkel D. Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol. 2003; 163: 1765-70.
54. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Bröcker EB, LeBoit PE, Pinkel D, Bastian BC. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005; 353: 2135-47.
55. Ackerman AB, David KM. A unifying concept of malignant melanoma: biologic aspects. Hum Pathol. 1986; 17: 438-40.
56. Feibleman CE, Stoll H, Maize JC. Melanomas of the palm, sole, and nailbed: a clinicopathologic study. Cancer. 1980; 46: 2492-504.
57. Kato T, Suetake T, Tabata N, Takahashi K, Tagami H. Epidemiology and prognosis of plantar melanoma in 62 Japanese patients over a 28-year period. Int J Dermatol. 1999; 38: 515-19.
58. Jimbow K, Takahashi H, Miura S, Ikeda S, Kukita A. Biological behavior and natural course of acral malignant melanoma. Clinical and histologic features and prognosis of palmoplantar, subungual, and other acral malignant melanomas. Am J Dermatopathol. 1984; 6 Suppl: 43-53.
59. Bradford PT, Goldstein AM, McMaster ML, Tucker MA. Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986-2005. Arch Dermatol. 2009; 145: 427-34.
60. Bastian BC, Kashani-Sabet M, Hamm H, Godfrey T, Moore DH 2nd, Bröcker EB, LeBoit PE, Pinkel D. Gene amplifications characterize acral melanoma and permit the detection of occult tumor cells in the surrounding skin. Cancer Res. 2000; 60: 1968-73.
61. Namiki T, Yanagawa S, Izumo T, Ishikawa M, Tachibana M, Kawakami Y, Yokozeki H, Nishioka K, Kaneko Y. Genomic alterations in primary cutaneous melanomas detected by metaphase comparative genomic hybridization with laser capture or manual microdissection: 6p gains may predict poor outcome. Cancer Genet Cytogenet. 2005; 157: 1-11.
62. Karlsson E, Waltersson MA, Bostner J, Pérez-Tenorio G, Olsson B, Hallbeck AL, Stål O. High-resolution genomic analysis of the 11q13 amplicon in breast cancers identifies synergy with 8p12 amplication, involving the mTOR targets S6K2 and 4EBP1. Genes Chromosomes Cancer. 2011;50: 775-87.
63. Sauter ER, Yeo UC, von Stemm A, Zhu W, Litwin S, Tichansky DS, Pistritto G, Nesbit M, Pinkel D, Herlyn M, Bastian BC. Cyclin D1 is a candidate oncogene in cutaneous melanoma. Cancer Res. 2002; 62: 3200-6.
64. Yamaura M, Takata M, Miyazaki A, Saida T. Specific dermoscopy patterns and amplifications of the cyclin D1 gene to define histopathologically unrecognizable early lesions of acral melanoma in situ. Arch Dermatol. 2005; 141: 1413-8.
65. Gast A, Scherer D, Chen B, Bloethner S, Melchert S, Sucker A, Hemminiki K, Schadendorf D, Kumar R. Somatic alterations in the melanoma genome: a highresolution array-based comparative genomic hybridization study. Genes Chromosomes Cancer. 2010; 49: 733-45.
66. Takata M, Goto Y, Ichii N, Yamamura M, Murata H, Koga H, Fujimoto A, Saida T. Constitutive activation of the mitogen-activated protein kinase signaling pathway in acral melanomas. J Invest Dermatol. 2005; 125: 318-22.
67. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006; 24: 4340-46.
68. Torres-Cabala CA, Wang WL, Trent J, Yang D, Chen S, Galbincea J, Kim KB, Woodman S, Davies M, Plaza JA, Nash JW, Prieto VG, Lazar AJ, Ivan D. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod Pathol. 2009; 22: 1446-56.
69. Kim KB, Eton O, Davis DW, Frazier ML, McConkey DJ, Diwan AH, Papadopoulos NE, Bedikian AY, Camacho LH, Ross MI, Cormier JN, Gershenwald JE, Lee JE, Mansfield PF, Billings LA, Ng CS, Charnsangavej C, Bar-Eli M, Johnson MM, Murgo AJ, Prieto VG. Phase II trial of imatinib mesylate in patients with metastatic melanoma. Br J Cancer. 2008; 99: 734-40.
70. Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastain BC, Schwartz GK. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011; 305: 2327-34.
71. Saldanha G, Potter L, Daforno P, Pringle JH. Cutaneous melanoma subtypes show different BRAF and NRAS mutation frequencies. Clin Cancer Res. 2006; 12: 4499-505.
72. Hawley SA, Davison M, Woods A, Davies SP, Beri RK, Carling D, Hardie DG. Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J Biol Chem. 1996; 271: 27879-87.
73. Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem. 2005; 280: 29060-66.
74. Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, Cantley LC. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA. 2004; 101: 3329-35.
75. Russell RR 3rd, Bergeron R, Shulman GI, Young LH. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am J Physiol. 1999; 277: H643-9.
76. Luo Z, Zang M, Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol. 2010; 6: 457-70.
77. Mirouse V, Billaud M. The LKB1/AMPK polarity pathway. FEBS Lett. 2011; 585: 981-5.
78. Yamamoto H, Takashima S, Shintani Y, Yamazaki S, Seguchi O, Nakano A, Higo S, Kato H, Liao Y, Asano Y, Minamino T, Matsumura Y, Takeda H, Kitakaze M. Identification of a novel substrate for TNFalpha-induced kinase NUAK2. Biochem Biophys Res Commun. 2008; 365: 541-7.
79. Hoppe PE, Chau J, Flanagan KA, Reedy AR, Schriefer LA. Caenorhabditis elegans unc-82 encodes a serine/threonine kinase important for myosin filament organization in muscle during growth. Genetics. 2010; 184: 79-90.
80. Vallenius T, Vaahtomeri K, Kovac B, Osiceanu AM, Viljanen M, Mäkelä TP. An association between NUAK2 and MRIP reveals a novel mechanism for regulation of actin stress fibers. J Cell Sci. 2011; 124: 384-93.
81. Lefebvre DL, Rosen CF. Regulation of SNARK activity in response to cellular stresses. Biochim Biophys Acta. 2005; 1724: 71-85.
82. Koh HJ, Toyoda T, Fujii N, Jung MM, Rathod A, Middelbeek RJ, Lessard SJ, Treebak JT, Tsuchihara K, Esumi H, Richter EA, Wojtaszewski JF, Hirshman MF, Goodyear LJ. Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle. Proc Natl Acad Sci USA. 2010; 107: 15541-6.
83. Tsuchihara K, Ogura T, Fujioka R, Fujii S, Kuga W, Saito M, Ochiya T, Ochiai A, Esumi H. Susceptibility of Snark-deficient mice to azoxymethane-induced colorectal tumorigenesis and the formation of aberrant crypt foci. Cancer Sci. 2008; 99: 677-82.
84. Legembre P, Schickel R, Barnhart BC, Peter ME. Identification of SNF1/AMP kinase-related kinase as an NF-kappaB-regulated anti-apoptotic kinase involved in CD95-induced motility and invasiveness. J Biol Chem. 2004; 279: 46742-47.
85. Noonan FP, Dudek J, Merlino G, De Fabo EC. Animal models of melanoma: an HGF/SF transgenic mouse model may facilitate experimental access to UV initiating events. Pigment Cell Res. 2003; 16: 16-25.
86. Esteve-Puig R, Canals F, Colomé N, Merlino G, Recio A. Uncoupling of the LKB1-AMPKalpha energy sensor pathway by growth factors and oncogenic BRAF. PLoS One. 2009; 4: e4771.
87. Zheng B, Jeong JH, Asara JM, Yuan YY, Granter SR, Chin L, Cantley LC. Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation. Mol Cell. 2009; 33: 237-47.
88. Wong SS, Rajakulendran S. Peutz-Jeghers syndrome associated with primary malignant melanoma of the rectum. Br J Dermatol. 1996; 135: 439-42.
89. Guldberg P, thor Straten P, Ahrenkiel V, Seremet T, Kirkin AF, Zeuthen J. Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma. Oncogene. 1999; 18: 1777-80.
90. Mungai PT, Waypa GB, Jairaman A, Prakriya M, Dokic D, Ball MK, Schumacker PT. Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels. Mol Cell Biol. 2011;31: 3531-45.
91. Gusarova GA, Trejo HE, Dada LA, Briva A, Welch LC, Hamanaka RB, Mutlu GM, Chandel NS, Prakriya M, Sznajder JI. Hypoxia leads to Na,K-ATPase downregulation via Ca2+ release-activated Ca2+ channels and AMPK activation. Mol Cell Biol. 2011;31: 3546-56.
92. Sealy RC, Hyde JS, Felix CC, Menon IA, Prota G, Swartz HM, Persad S, Haberman HF. Novel free radicals in synthetic and natural pheomelanins: distinction between dopa melanin and cysteinyldopa melanins by ESR spectroscopy. Proc Natl Acad Sci USA. 1982; 79: 2885-9.
93. Bedogni B, Welford SM, Cassarino DS, Nickoloff BJ, Giaccia AJ, Powell MB. The hypoxic microenvironment of the skin contributes to Akt-mediated melanocyte transformation. Cancer Cell. 2005; 8: 443-54.
94. Leontieva OV, Blaqosklonny MV. DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence. Aging (Albany NY). 2010; 2: 924-35.
95. Korotchkina LG, Leontieva OV, Bukreeva EI, Demidenko ZN, Gudkov AV, Blaqosklonny MV. The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway. Aging (Albany NY). 2010; 2: 344-52.
96. Koomen JM, Smalley KS. Using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma. Oncotarget. 2011; 2: 329-35.
97. Beloueche-Babari M, Arunan V, Jackson LE, Perusinqhe N, Sharp SY, Workman P, Leach MO. Modulation of melanoma cell phospholipid metabolism in response to heat shock protein 90 inhibition. Oncotarget. 2010; 1: 185-97.
98. Ugurel S, Hildenbrand R, Zimpfer A, La Rosée P, Paschka P, Sucker A, Keikavoussi P, Becker JC, Rittgen W, Hochhaus A, Schadendorf D. Lack of clinical efficacy of imatinib in metastatic melanoma. Br J Cancer. 2005; 92: 1398-405.