Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity

EMBO Journal

Volumn 34, Issue 4, 2015, Pages 517-530

  Singh, Shiv K ^a   Chen, Nai Ming ^b   Hessmann, Elisabeth ^b   Siveke, Jens ^c   Lahmann, Marlen ^a   Singh, Garima ^a   Voelker, Nadine ^a   Vogt, Sophia ^a   Esposito, Irene ^d   Schmidt, Ansgar ^e   Brendel, Cornelia ^a   Stiewe, Thorsten ^a   Gaedcke, Jochen ^b   Mernberger, Marco ^a   Crawford, Howard C ^f   Bamlet, William R ^g   Zhang, Jin San ^h,i   Li, Xiao Kun ⁱ   Smyrk, Thomas C ^h   Billadeau, Daniel D ^h   Hebrok, Matthias ^j   Neesse, Albrecht ^b   Koenig, Alexander ^b,h   Ellenrieder, Volker ^b   more..

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^c TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^d INSTITUTE OF EPIDEMIOLOGY   (Germany)

^e UNIVERSITY HOSPITAL MARBURG   (Germany)

^f MAYO CLINIC   (United States)

^g Mayo Clinic   (United States)

^h MAYO CLINIC   (United States)

ⁱ WENZHOU MEDICAL UNIVERSITY   (China)

^j and Human Genetics   (United States)

more..

Author keywords

Cellular plasticity; miRNA; NFATc1; p53; Sox2

Indexed keywords

MICRORNA 200; MICRORNA 200C; PROTEIN P53; RNA POLYMERASE II; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NFATC1; TRANSCRIPTION FACTOR SOX2; UNCLASSIFIED DRUG; MICRORNA; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR SOX;

ABDOMINAL DISTENSION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CACHEXIA; CANCER CELL; CANCER STEM CELL; CARCINOGENESIS; CELL DEDIFFERENTIATION; CELL MIGRATION; CHROMATIN IMMUNOPRECIPITATION; COMPLEX FORMATION; ENHANCER REGION; EPITHELIUM CELL; GENE CONTROL; GENE DISRUPTION; GENE SEQUENCE; GENOTYPE; HUMAN; HUMAN CELL; HUMAN TISSUE; MOUSE; NONHUMAN; PANCREAS ADENOCARCINOMA; PANCREAS CANCER; PANCREAS CELL; PHENOTYPE; PLASTICITY; PRIORITY JOURNAL; PROMOTER REGION; SIGNAL TRANSDUCTION; UPREGULATION; WESTERN BLOTTING; ANIMAL; CELL DIFFERENTIATION; EPITHELIAL MESENCHYMAL TRANSITION; GENETICS; METABOLISM; PANCREAS TUMOR; PHYSIOLOGY; TUMOR CELL LINE;

ANIMALS; CELL DIFFERENTIATION; CELL LINE, TUMOR; EPITHELIAL-MESENCHYMAL TRANSITION; HUMANS; MICE; MICRORNAS; NFATC TRANSCRIPTION FACTORS; PANCREATIC NEOPLASMS; SOXB1 TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84923050071     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.15252/embj.201489574     Document Type: Article

References (53)

1. Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T (2005) Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer 5: 744-749
2. Brabletz S, Bajdak K, Meidhof S, Burk U, Niedermann G, Firat E, Wellner U, Dimmler A, Faller G, Schubert J, Brabletz T (2011) The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells. EMBO J 30: 770-782
3. Baumgart S, Glesel E, Singh G, Chen N-M, Reutlinger K, Zhang J, Billadeau DD, Fernandez-Zapico ME, Gress TM, Singh SK, Ellenrieder V (2012) Restricted heterochromatin formation links NFATc 2 repressor activity with growth promotion in pancreatic cancer. Gastroenterology 142: 388-398
4. Brabletz T (2012 ) EMT and MET in metastasis: where are the cancer stem cells? Cancer Cell 22: 699-701
5. Baumgart S, Chen N-M, Siveke JT, König A, Zhang J-S, Singh SK, Wolf E, Bartkuhn M, Esposito I, Heinnodatabetamann E, Reinecke J, Nikorowitsch J, Brunner M, Singh G, Fernandez-Zapico ME, Smyrk T, Bamlet WR, Eilers M, Neesse A, Gress TM et al (2014) Inflammation-induced NFATc1-STAT3 transcription complex promotes pancreatic cancer initiation by KrasG12D. Cancer Discov 4: 688-701
6. Buchholz M, Schatz A, Wagner M, Michl P, Linhart T, Adler G, Gress TM, Ellenrieder V (2006) Overexpression of c-myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway. EMBO J 25: 3714-3724
7. Chang C-J, Chao C-H, Xia W, Yang J-Y, Xiong Y, Li C-W, Yu W-H, Rehman SK, Hsu JL, Lee H-H, Liu M, Chen C-T, Yu D, Hung M-C (2011a) p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 13: 317-323
8. Chang S-C, Mulloy B, Magee AI, Couchman JR (2011b) Two distinct sites in sonic Hedgehog combine for heparan sulfate interactions and cell signaling functions. J Biol Chem 286: 44391-44402
9. Choi YJ, Lin C-P, Ho JJ, He X, Okada N, Bu P, Zhong Y, Kim SY, Bennett MJ, Chen C, Ozturk A, Hicks GG, Hannon GJ, He L (2011) miR-34 miRNAs provide a barrier for somatic cell reprogramming. Nat Cell Biol 13: 1353-1360
10. Cox JL, Wilder PJ, Desler M, Rizzino A (2012) Elevating SOX2 levels deleteriously affects the growth of medulloblastoma and glioblastoma cells. PLoS ONE 7: e44087
11. Gu G, Wells JM, Dombkowski D, Preffer F, Aronow B, Melton DA (2004) Global expression analysis of gene regulatory pathways during endocrine pancreatic development. Development 131: 165-179
12. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144: 646-674
13. Herreros-Villanueva M, Zhang J-S, Koenig A, Abel EV, Smyrk TC, Bamlet WR, de Narvajas AA-M, Gomez TS, Simeone DM, Bujanda L, Billadeau DD (2013) SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells. Oncogenesis 2: e61
14. Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, DePinho RA (2006) Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev 20: 1218-1249
15. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, Rustgi AK, Chang S, Tuveson DA (2005) Trp53R 172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7: 469-483
16. Hogan PG, Chen L, Nardone J, Rao A (2003) Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev 17: 2205-2232
17. Huth J, Buchholz M, Kraus JM, Schmucker M, von Wichert G, Krndija D, Seufferlein T, Gress TM, Kestler HA (2010) Significantly improved precision of cell migration analysis in time-lapse video microscopy through use of a fully automated tracking system. BMC Cell Biol 11: 24
18. Huth J, Buchholz M, Kraus JM, Mølhave K, Gradinaru C, von Wichert G, Gress TM, Neumann H, Kestler HA (2011) TimeLapseAnalyzer: multi-target analysis for live-cell imaging and time-lapse microscopy. Comput Methods Programs Biomed 104: 227-234
19. Imamichi Y, König A, Gress T, Menke A (2007) Collagen type I-induced Smad-interacting protein 1 expression downregulates E-cadherin in pancreatic cancer. Oncogene 26: 2381-2385
20. Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, Jacks T, Tuveson DA (2001) Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 15: 3243-3248
21. Jauliac S, López-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A (2002) The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Nat Cell Biol 4: 540-544
22. Kao S-C, Wu H, Xie J, Chang C-P, Ranish JA, Graef IA, Crabtree GR (2009) Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation. Science 323: 651-654
23. Kapoor A, Yao W, Ying H, Hua S, Liewen A, Wang Q, Zhong Y, Wu C-J, Sadanandam A, Hu B, Chang Q, Chu GC, Al-Khalil R, Jiang S, Xia H, Fletcher-Sananikone E, Lim C, Horwitz GI, Viale A, Pettazzoni P et al (2014) Yap1 activation enables bypass of oncogenic kras addiction in pancreatic cancer. Cell 158: 185-197
24. Kent OA, Mullendore M, Wentzel EA, López-Romero P, Tan AC, Alvarez H, West K, Ochs MF, Hidalgo M, Arking DE, Maitra A, Mendell JT (2009) A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells. Cancer Biol Ther 8: 2013-2024
25. Kim NH, Kim HS, Li X-Y, Lee I, Choi H-S, Kang SE, Cha SY, Ryu JK, Yoon D, Fearon ER, Rowe RG, Lee S, Maher CA, Weiss SJ, Yook JI (2011a) A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J Cell Biol 195: 417-433
26. Kim T, Veronese A, Pichiorri F, Lee TJ, Jeon Y-J, Volinia S, Pineau P, Marchio A, Palatini J, Suh S-S, Alder H, Liu C-G, Dejean A, Croce CM (2011b) p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB 2. J Exp Med 208: 875-883
27. Koenig A, Linhart T, Schlengemann K, Reutlinger K, Wegele J, Adler G, Singh G, Hofmann L, Kunsch S, Büch T, Schäfer E, Gress TM, Fernandez-Zapico ME, Ellenrieder V (2010) NFAT-induced histone acetylation relay switch promotes c-Myc-dependent growth in pancreatic cancer cells. Gastroenterology 138: 1189-1199
28. König A, Fernandez-Zapico ME, Ellenrieder V (2010 ) Primers on molecular pathways - the NFAT transcription pathway in pancreatic cancer. Pancreatology 10: 416-422
29. Lagunas L, Clipstone NA (2009) Deregulated NFATc 1 activity transforms murine fibroblasts via an autocrine growth factor-mediated Stat3-dependent pathway. J Cell Biochem 108: 237-248
30. Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15: 178-196
31. Leis O, Eguiara A, Lopez-Arribillaga E, Alberdi MJ, Hernandez-Garcia S, Elorriaga K, Pandiella A, Rezola R, Martin AG (2012) Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene 31: 1354-1365
32. Li X, Zhu L, Yang A, Lin J, Tang F, Jin S, Wei Z, Li J, Jin Y (2011) Calcineurin-NFAT signaling critically regulates early lineage specification in mouse embryonic stem cells and embryos. Cell Stem Cell 8: 46-58
33. Liu Y, Sánchez-Tilló E, Lu X, Huang L, Clem B, Telang S, Jenson AB, Cuatrecasas M, Chesney J, Postigo A, Dean DC (2014) The ZEB1 transcription factor acts in a negative feedback loop with miR200 downstream of Ras and Rb1 to regulate Bmi1 expression. J Biol Chem 289: 4116-4125
34. Lu Y-X, Yuan L, Xue X-L, Zhou M, Liu Y, Zhang C, Li J-P, Zheng L, Hong M, Li X-N (2014 ) Regulation of colorectal carcinoma stemness, growth, and metastasis by an miR-200c-Sox2-negative feedback loop mechanism. Clin Cancer Res 20: 2631-2642
35. Maitra A, Hruban RH (2008) Pancreatic cancer. Annu Rev Pathol 3: 157-188
36. Meuwissen R, Linn SC, Linnoila RI, Zevenhoven J, Mooi WJ, Berns A (2003) Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 4: 181-189
37. Morton JP, Karim SA, Graham K, Timpson P, Jamieson N, Athineos D, Doyle B, McKay C, Heung M-Y, Oien KA, Frame MC, Evans TRJ, Sansom OJ, Brunton VG (2010) Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology 139: 292-303
38. Nagamoto-Combs K, Combs CK (2010) Microglial phenotype is regulated by activity of the transcription factor, NFAT (nuclear factor of activated T cells). J Neurosci 30: 9641-9646
39. Nakhai H, Siveke JT, Mendoza-Torres L, Schmid RM (2008) Conditional inactivation of Myc impairs development of the exocrine pancreas. Development 135: 3191-3196
40. Pinho AV, Rooman I, Real FX (2011a) p53-dependent regulation of growth, epithelial-mesenchymal transition and stemness in normal pancreatic epithelial cells. Cell Cycle 10: 1312-1321
41. Pinho AV, Rooman I, Reichert M, De Medts N, Bouwens L, Rustgi AK, Real FX (2011b) Adult pancreatic acinar cells dedifferentiate to an embryonic progenitor phenotype with concomitant activation of a senescence programme that is present in chronic pancreatitis. Gut 60: 958-966
42. Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9: 265-273
43. Rao A, Luo C, Hogan PG (1997) Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 15: 707-747
44. Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, Reichert M, Beatty GL, Rustgi AK, Vonderheide RH, Leach SD, Stanger BZ (2012) EMT and dissemination precede pancreatic tumor formation. Cell 148: 349-361
45. Rhim AD, Thege FI, Santana SM, Lannin TB, Saha TN, Tsai S, Maggs LR, Kochman ML, Ginsberg GG, Lieb JG, Chandrasekhara V, Drebin JA, Ahmad N, Yang Y-X, Kirby BJ, Stanger BZ (2014) Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions. Gastroenterology 146: 647-651
46. Rustgi AK (2006 ) The molecular pathogenesis of pancreatic cancer: clarifying a complex circuitry. Genes Dev 20: 3049-3053
47. Sánchez-Tilló E, Liu Y, de Barrios O, Siles L, Fanlo L, Cuatrecasas M, Darling DS, Dean DC, Castells A, Postigo A (2012) EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci 69: 3429-3456
48. Sarkar A, Hochedlinger K (2013) The sox family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell 12: 15-30
49. Schlereth K, Beinoraviciute-Kellner R, Zeitlinger MK, Bretz AC, Sauer M, Charles JP, Vogiatzi F, Leich E, Samans B, Eilers M, Kisker C, Rosenwald A, Stiewe T (2010) DNA binding cooperativity of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell 38: 356-368
50. Spike BT, Wahl GM (2011) p53, stem cells, and reprogramming: tumor suppression beyond guarding the genome. Genes Cancer 2: 404-419
51. Szychot E, Brodkiewicz A, Peregud-Pogorzelski J (2013) Will therapies that target tumour suppressor genes be useful in cancer treatment? Adv Clin Exp Med 22: 861-864
52. Thiery J-P (2009) [Epithelial-mesenchymal transitions in cancer onset and progression]. Bull Acad Natl Med 193: 1969-1978, discussion 1978-1979
53. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, Hausen zur A, Brunton VG, Morton J, Sansom O, Schüler J, Stemmler MP, Herzberger C, Hopt U, Keck T, Brabletz S, Brabletz T (2009) The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 11: 1487-1495