KSR1 is overexpressed in endometrial carcinoma and regulates proliferation and TRAIL-induced apoptosis by modulating FLIP levels

American Journal of Pathology

Volumn 178, Issue 4, 2011, Pages 1529-1543

  Llobet, David ^a   Eritja, Nuria ^a   Domingo, Monica ^a   Bergada, Laura ^a   Mirantes, Cristina ^a   Santacana, Maria ^a   Pallares, Judit ^a   Macià, Anna ^b   Yeramian, Andree ^a   Encinas, Mario ^b   Moreno Bueno, Gema ^c   Palacios, Jose ^d   Lewis, Robert E ^e   Matias Guiu, Xavier ^a   Dolcet, Xavi ^a  

^a HOSPITAL UNIVERSITARI ARNAU DE VILANOVA   (Spain)

^b UNIVERSITY OF LLEIDA   (Spain)

^c INSTITUTO DE INVESTIGACIONES BIOMÉDICAS ALBERTO SOLS   (Spain)

^d HOSPITAL UNIVERSITARIO VIRGEN DEL ROCÍO   (Spain)

^e UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY DNA; FAS ANTIBODY; FAS LIGAND; FLICE INHIBITORY PROTEIN; KINASE SUPPRESSOR OF RAS 1; PROTEIN KINASE INHIBITOR; SHORT HAIRPIN RNA; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG;

ADULT; APOPTOSIS; ARTICLE; CANCER CELL; CANCER INHIBITION; CARCINOGENESIS; CELL ANCHORAGE; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; ENDOMETRIUM CARCINOMA; ENDOMETRIUM CELL; ENZYME INHIBITION; FEMALE; GENETIC TRANSCRIPTION; GROWTH REGULATION; HUMAN; HUMAN CELL; MOLECULAR MECHANICS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; SENSITIZATION; TISSUE MICROARRAY; TRANSLATION REGULATION; UPREGULATION;

EID: 79953672942     PISSN: 00029440     EISSN: 15252191     Source Type: Journal    
DOI: 10.1016/j.ajpath.2010.12.041     Document Type: Article

References (72)

1. Chang L, Karin M: Mammalian MAP kinase signaling cascades. Nature 2001, 410:37-40 (Pubitemid 32225829)
2. Morrison DK: KSR: a MAPK scaffold of the Ras pathway? J Cell Sci 2001, 114:1609-1612
3. Kornfeld K, Hom DB, Horvitz HR: The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated signaling in C. elegans. Cell 1995, 83:903-913 (Pubitemid 26006532)
4. Sundaram M, Han M: The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras-mediated signal transduction. Cell 1995, 83:889-901 (Pubitemid 26006531)
5. Therrien M, Chang HC, Solomon NM, Karim FD, Wassarman DA, Rubin GM: KSR, a novel protein kinase required for RAS signal transduction. Cell 1995, 83:879-888 (Pubitemid 26006530)
6. Therrien M, Michaud NR, Rubin GM, Morrison DK: KSR modulates signal propagation within the MAPK cascade. Genes Dev 1996, 10:2684-2695 (Pubitemid 26384489)
7. Nguyen A, Burack WR, Stock JL, Kortum R, Chaika OV, Afkarian M, Muller WJ, Murphy KM, Morrison DK, Lewis RE, McNeish J, Shaw AS: Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo. Mol Cell Biol 2002, 22:3035-3045 (Pubitemid 34437462)
8. Roy F, Laberge G, Douziech M, Ferland-McCollough D, Therrien M: KSR is a scaffold required for activation of the ERK/MAPK module. Genes Dev 2002, 16:427-438 (Pubitemid 34165100)
9. Kortum RL, Lewis RE: The molecular scaffold KSR1 regulates the proliferative and oncogenic potential of cells. Mol Cell Biol 2004, 24:4407-4416 (Pubitemid 41071010)
10. Kolch W: Coordinating ERK/MAPK signaling through scaffolds and inhibitors. Nat Rev Mol Cell Biol 2005, 6:827-837
11. Joneson T, Fulton JA, Volle DJ, Chaika OV, Bar-Sagi D, Lewis RE: Kinase suppressor of Ras inhibits the activation of extracellular ligand-regulated (ERK) mitogen-activated protein (MAP) kinase by growth factors, activated Ras, and Ras effectors. J Biol Chem 1998, 273:7743-7748 (Pubitemid 28152806)
12. Razidlo GL, Kortum RL, Haferbier JL, Lewis RE: Phosphorylation regulates KSR1 stability, ERK activation, and cell proliferation. J Biol Chem 2004, 279:47808-47814 (Pubitemid 39540930)
13. Lozano J, Xing R, Cai Z, Jensen HL, Trempus C, Mark W, Cannon R, Kolesnick R: Deficiency of kinase suppressor of Ras1 prevents oncogenic ras signaling in mice. Cancer Res 2003, 63:4232-4238 (Pubitemid 36917951)
14. Xing HR, Cordon-Cardo C, Deng XZ, Tong W, Campodonico L, Fuks Z, Kolesnick R: Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer. Nat Med 2003, 9:1266-1268 (Pubitemid 37279848)
15. McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, Stivala F, Libra M, Basecke J, Evangelisti C, Martelli AM, Franklin RA: Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007, 1773:1263-1284 (Pubitemid 47125967)
16. Kolesnick R, Xing HR: Inflammatory bowel disease reveals the kinase activity of KSR1. J Clin Invest 2004, 114:1233-1237 (Pubitemid 40385292)
17. Yan F, John SK, Wilson G, Jones DS, Washington MK, Polk DB: Kinase suppressor of Ras-1 protects intestinal epithelium from cytokine-mediated apoptosis during inflammation. J Clin Invest 2004, 114:1272-1280 (Pubitemid 40385298)
18. Dolcet X, Llobet D, Pallares J, Rue M, Comella JX, Matias-Guiu X: FLIP is frequently expressed in endometrial carcinoma and has a role in resistance to TRAIL-induced apoptosis. Lab Invest 2005, 85:885-894 (Pubitemid 41021297)
19. Llobet D, Eritja N, Encinas M, Llecha N, Yeramian A, Pallares J, Sorolla A, Gonzalez-Tallada FJ, Matias-Guiu X, Dolcet X: CK2 controls TRAIL and Fas sensitivity by regulating FLIP levels in endometrial carcinoma cells. Oncogene 2008, 27:2513-2524 (Pubitemid 351550887)
20. Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH: Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 1999, 104:155-162
21. Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH: Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 1999, 5:157-163 (Pubitemid 29068521)
22. Koschny R, Walczak H, Ganten TM: The promise of TRAIL: potential and risks of a novel anticancer therapy. J Mol Med 2007, 85:923-935 (Pubitemid 47282789)
23. Johnstone RW, Frew AJ, Smyth MJ: The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer 2008, 8:782-798
24. LeBlanc HN, Ashkenazi A: Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ 2003, 10:66-75 (Pubitemid 36511833)
25. Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT: TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 1997, 16:5386-5397 (Pubitemid 27380146)
26. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A: Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 1997, 277:818-821 (Pubitemid 27366733)
27. Bodmer JL, Holler N, Reynard S, Vinciguerra P, Schneider P, Juo P, Blenis J, Tschopp J: TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol 2000, 2:241-243
28. Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A: Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 2000, 12:611-620
29. Sprick MR, Weigand MA, Rieser E, Rauch CT, Juo P, Blenis J, Krammer PH, Walczak H: FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity 2000, 12:599-609
30. Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson DW, Briand C, Grutter MG: The long form of FLIP is an activator of caspase-8 at the fas death-inducing signaling complex. J Biol Chem 2002, 277:45162-45171 (Pubitemid 36159119)
31. Irmler M, Steiner V, Ruegg C, Wajant H, Tschopp J: Caspase-induced inactivation of the anti-apoptotic TRAF1 during Fas ligand-mediated apoptosis. FEBS Lett 2000, 468:129-133 (Pubitemid 30110781)
32. Moreno-Bueno G, Sanchez-Estevez C, Cassia R, Rodriguez-Perales S, Diaz-Uriarte R, Dominguez O, Hardisson D, Andujar M, Prat J, Matias-Guiu X, Cigudosa JC, Palacios J: Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: sTK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res 2003, 63:5697-5702 (Pubitemid 37187463)
33. Llobet D, Pallares J, Yeramian A, Santacana M, Eritja N, Velasco A, Dolcet X, Matias-Guiu X: Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. J Clin Pathol 2000, 62:777-785
34. Pallares J, Llobet D, Santacana M, Eritja N, Velasco A, Cuevas D, Lopez S, Palomar-Asenjo V, Yeramian A, Dolcet X, Matias-Guiu X: CK2beta is expressed in endometrial carcinoma and has a role in apoptosis resistance and cell proliferation. Am J Pathol 2009, 174:287-296
35. Pallares J, Martinez-Guitarte JL, Dolcet X, Llobet D, Rue M, Palacios J, Prat J, Matias-Guiu X: Survivin expression in endometrial carcinoma: a tissue microarray study with correlation with PTEN and STAT-3. Int J Gynecol Pathol 2005, 24:247-253 (Pubitemid 40885078)
36. Dolcet X, Llobet D, Encinas M, Pallares J, Cabero A, Schoenenberger JA, Comella JX, Matias-Guiu X: Proteasome inhibitors induce death but activate NF-kappaB on endometrial carcinoma cell lines and primary culture explants. J Biol Chem 2006, 281:22118-22130 (Pubitemid 44181916)
37. Padmanabha R, Chen-Wu JL, Hanna DE, Glover CV: Isolation, sequencing, and disruption of the yeast CKA2 gene: casein kinase II is essential for viability in Saccharomyces cerevisiae. Mol Cell Biol 1990, 10:4089-4099
38. Kikkawa U, Mann SK, Firtel RA, Hunter T: Molecular cloning of casein kinase II alpha subunit from Dictyostelium discoideum and its expression in the life cycle. Mol Cell Biol 1992, 12:5711-5723
39. Allende JE, Allende CC: Protein kinases. 4. Protein kinase CK2: an enzyme with multiple substrates and a puzzling regulation. FASEB J 1995, 9:313-323
40. Ahmed K, Gerber DA, Cochet C: Joining the cell survival squad: an emerging role for protein kinase CK2. Trends Cell Biol 2002, 12:226-230
41. Litchfield DW: Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J 2003, 369:1-15
42. Tawfic S, Yu S, Wang H, Faust R, Davis A, Ahmed K: Protein kinase CK2 signal in neoplasia. Histol Histopathol 2001, 16:573-582 (Pubitemid 32297655)
43. Kim Y, Suh N, Sporn M, Reed JC: An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. J Biol Chem 2002, 277:22320-22329 (Pubitemid 34967199)
44. Poukkula M, Kaunisto A, Hietakangas V, Denessiouk K, Katajamaki T, Johnson MS, Sistonen L, Eriksson JE: Rapid turnover of c-FLIPshort is determined by its unique C-terminal tail. J Biol Chem 2005, 280:27345-27355 (Pubitemid 41040776)
45. Chang L, Kamata H, Solinas G, Luo JL, Maeda S, Venuprasad K, Liu YC, Karin M: The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. Cell 2006, 124:601-613
46. Velasco A, Bussaglia E, Pallares J, Dolcet X, Llobet D, Encinas M, Llecha N, Palacios J, Prat J, Matias-Guiu X: PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS alterations. Hum Pathol 2006, 37:1465-1472 (Pubitemid 44584324)
47. Pallares J, Velasco A, Eritja N, Santacana M, Dolcet X, Cuatrecasas M, Palomar-Asenjo V, Catasus L, Prat J, Matias-Guiu X: Promoter hypermethylation and reduced expression of RASSF1A are frequent molecular alterations of endometrial carcinoma. Mod Pathol 2008, 21:691-699 (Pubitemid 351744834)
48. Lagarda H, Catasus L, Arguelles R, Matias-Guiu X, Prat J: K-ras mutations in endometrial carcinomas with microsatellite instability. J Pathol 2001, 193:193-199 (Pubitemid 32118131)
49. Razidlo GL, Johnson HJ, Stoeger SM, Cowan KH, Bessho T, Lewis RE: KSR1 is required for cell cycle reinitiation following DNA damage. J Biol Chem 2009, 284:6705-6715
50. Kim M, Yan Y, Kortum RL, Stoeger SM, Sgagias MK, Lee K, Lewis RE, Cowan KH: Expression of kinase suppressor of Ras1 enhances cisplatin-induced extracellular signal-regulated kinase activation and cisplatin sensitivity. Cancer Res 2005, 65:3986-3992 (Pubitemid 40775633)
51. Dolcet X, Llobet D, Pallares J, Matias-Guiu X: NF-kB in development and progression of human cancer. Virchows Arch 2005, 446:475-482 (Pubitemid 40884279)
52. Duiker EW, Mom CH, de Jong S, Willemse PH, Gietema JA, van der Zee AG, de Vries EG: The clinical trail of TRAIL. Eur J Cancer 2006, 42:2233-2240 (Pubitemid 44307615)
53. Carlo-Stella C, Lavazza C, Locatelli A, Vigano L, Gianni AM, Gianni L: Targeting TRAIL agonistic receptors for cancer therapy. Clin Cancer Res 2007, 13:2313-2317 (Pubitemid 46698578)
54. Falschlehner C, Emmerich CH, Gerlach B, Walczak H: TRAIL signaling: decisions between life and death. Int J Biochem Cell Biol 2007, 39:1462-1475 (Pubitemid 47031030)
55. Rippo MR, Moretti S, Vescovi S, Tomasetti M, Orecchia S, Amici G, Catalano A, Procopio A: FLIP overexpression inhibits death receptor-induced apoptosis in malignant mesothelial cells. Oncogene 2004, 23:7753-7760 (Pubitemid 39457025)
56. Lee SH, Kim HS, Kim SY, Lee YS, Park WS, Kim SH, Lee JY, Yoo NJ: Increased expression of FLIP, an inhibitor of Fas-mediated apoptosis, in stomach cancer. Apmis 2003, 111:309-314 (Pubitemid 36560548)
57. Korkolopoulou P, Goudopoulou A, Voutsinas G, Thomas-Tsagli E, Kapralos P, Patsouris E, Saetta AA: c-FLIP expression in bladder urothelial carcinomas: its role in resistance to Fas-mediated apoptosis and clinicopathologic correlations. Urology 2004, 63:1198-1204 (Pubitemid 38746841)
58. Dutton A, O'Neil JD, Milner AE, Reynolds GM, Starczynski J, Crocker J, Young LS, Murray PG: Expression of the cellular FLICE-inhibitory protein (c-FLIP) protects Hodgkin's lymphoma cells from autonomous Fas-mediated death. Proc Natl Acad Sci USA 2004, 101:6611-6616 (Pubitemid 38586022)
59. Zhang X, Jin TG, Yang H, DeWolf WC, Khosravi-Far R, Olumi AF: Persistent c-FLIP(L) expression is necessary and sufficient to maintain resistance to tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in prostate cancer. Cancer Res 2004, 64:7086-7091
60. Rosato RR, Almenara JA, Coe S, Grant S: The multikinase inhibitor sorafenib potentiates TRAIL lethality in human leukemia cells in association with Mcl-1 and cFLIPL down-regulation. Cancer Res 2007, 67:9490-9500 (Pubitemid 47535939)
61. Panner A, Parsa AT, Pieper RO: Translational regulation of TRAIL sensitivity. Cell Cycle 2006, 5:147-150 (Pubitemid 43131148)
62. Panner A, Nakamura JL, Parsa AT, Rodriguez-Viciana P, Berger MS, Stokoe D, Pieper RO: mTOR-independent translational control of the extrinsic cell death pathway by RalA. Mol Cell Biol 2006, 26:7345-7357 (Pubitemid 44547688)
63. Panner A, James CD, Berger MS, Pieper RO: mTOR controls FLIPS translation and TRAIL sensitivity in glioblastoma multiforme cells. Mol Cell Biol 2005, 25:8809-8823 (Pubitemid 41429073)
64. Ley R, Balmanno K, Hadfield K, Weston C, Cook SJ: Activation of the ERK1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein, Bim. J Biol Chem 2003, 278:18811-18816 (Pubitemid 36799262)
65. Corazza N, Jakob S, Schaer C, Frese S, Keogh A, Stroka D, Kassahn D, Torgler R, Mueller C, Schneider P, Brunner T: TRAIL receptor-mediated JNK activation and Bim phosphorylation critically regulate Fas-mediated liver damage and lethality. J Clin Invest 2006, 116:2493-2499 (Pubitemid 44330148)
66. Han J, Goldstein LA, Gastman BR, Rabinowich H: Interrelated roles for Mcl-1 and BIM in regulation of TRAIL-mediated mitochondrial apoptosis. J Biol Chem 2006, 281:10153-10163 (Pubitemid 43864551)
67. Llobet D, Eritja N, Yeramian A, Pallares J, Sorolla A, Domingo M, Santacana M, Gonzalez-Tallada FJ, Matias-Guiu X, Dolcet X: The multikinase inhibitor sorafenib induces apoptosis and sensitises endometrial cancer cells to TRAIL by different mechanisms. Eur J Cancer 46:836-850
68. Krueger A, Schmitz I, Baumann S, Krammer PH, Kirchhoff S: Cellular FLICE-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death-inducing signaling complex. J Biol Chem 2001, 276:20633-20640
69. Kataoka T, Tschopp J: N-terminal fragment of c-FLIP(L) processed by caspase 8 specifically interacts with TRAF2 and induces activation of the NF-kappa B signaling pathway. Mol Cell Biol 2004, 24:2627-2636
70. Ritt DA, Zhou M, Conrads TP, Veenstra TD, Copeland TD, Morrison DK: CK2 Is a component of the KSR1 scaffold complex that contributes to Raf kinase activation. Curr Biol 2007, 17:179-184 (Pubitemid 46107825)
71. Xing HR, Campodonico L, Kolesnick R: The kinase activity of kinase suppressor of Ras1 (KSR1) is independent of bound MEK. J Biol Chem 2004, 279:26210-26214 (Pubitemid 38798767)
72. Xing HR, Kolesnick R: Kinase suppressor of Ras signals through Thr269 of c-Raf-1. J Biol Chem 2001, 276:9733-9741 (Pubitemid 37391870)