Transcription factor PREP1 induces EMT and metastasis by controlling the TGF-β-SMAD3 pathway in non-small cell lung adenocarcinoma

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 36, 2014, Pages E3775-E3784

  Risolino, Maurizio ^a   Mandia, Nadia ^a,b   Iavarone, Francescopaolo ^a   Dardaei, Leila ^b   Longobardi, Elena ^b   Fernandez, Serena ^a   Talotta, Francesco ^a   Bianchi, Fabrizio ^b,c   Pisati, Federica ^b   Spaggiari, Lorenzo ^c   Harter, Patrick N ^d   Mittelbronn, Michel ^d   Schulte, Dorothea ^d   Incoronato, Mariarosaria ^e   Di Fiore, Pier Paolo ^b,c   Blasi, Francesco ^b   Verde, Pasquale ^a,e  

^a INSTITUTE OF GENETICS AND BIOPHYSICS ADRIANO BUZZATI TRAVERSO   (Italy)

^b FIRC INSTITUTE OF MOLECULAR ONCOLOGY   (Italy)

^c UNIVERSITY OF MILAN   (Italy)

^d Institute of Neurology (Edinger Institute)   (Germany)

^e IRCCS SDN   (Italy)

Author keywords

PTGF ; TALE proteins

Indexed keywords

DNA BINDING PROTEIN; HOMEODOMAIN PROTEIN; ONCOPROTEIN; PBX1 PROTEIN, HUMAN; PEPTIDE HYDROLASE; PKNOX1 PROTEIN, HUMAN; PROTEIN BINDING; PROTEIN C FOS; SMAD3 PROTEIN; SMAD3 PROTEIN, HUMAN; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR FRA 1; TRANSFORMING GROWTH FACTOR BETA;

ADENOCARCINOMA; ANIMAL; BIOLOGICAL MODEL; BRAIN TUMOR; CELL MOTION; CELL NUCLEUS; CELL PROLIFERATION; DRUG EFFECTS; ENHANCER REGION; EPITHELIAL MESENCHYMAL TRANSITION; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; HUMAN; INTRON; LUNG TUMOR; METABOLISM; METASTASIS; MOUSE; NON SMALL CELL LUNG CANCER; PATHOLOGY; SECONDARY; SIGNAL TRANSDUCTION; SURVIVAL; TUMOR CELL LINE;

ADENOCARCINOMA; ANIMALS; BRAIN NEOPLASMS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CELL MOVEMENT; CELL NUCLEUS; CELL PROLIFERATION; DNA-BINDING PROTEINS; ENHANCER ELEMENTS, GENETIC; EPITHELIAL-MESENCHYMAL TRANSITION; GENE EXPRESSION REGULATION, NEOPLASTIC; HOMEODOMAIN PROTEINS; HUMANS; INTRONS; LUNG NEOPLASMS; MICE; MODELS, BIOLOGICAL; NEOPLASM METASTASIS; PEPTIDE HYDROLASES; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-FOS; SIGNAL TRANSDUCTION; SMAD3 PROTEIN; SURVIVAL ANALYSIS; TRANSCRIPTION FACTOR AP-1; TRANSCRIPTION, GENETIC; TRANSFORMING GROWTH FACTOR BETA;

EID: 84907006054     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1407074111     Document Type: Article

References (50)

1. Berthelsen J, Zappavigna V, Ferretti E, Mavilio F, Blasi F (1998) The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity. EMBO J 17(5):1434-1445.
2. Fernandez-Diaz LC, et al. (2010) The absence of Prep1 causes p53-dependent apoptosis of mouse pluripotent epiblast cells. Development 137(20):3393-3403.
3. Ferretti E, et al. (2006) Hypomorphic mutation of the TALE gene Prep1 (pKnox1) causes a major reduction of Pbx and Meis proteins and a pleiotropic embryonic phenotype. Mol Cell Biol 26(15):5650-5662.
4. Micali N, et al. (2010) Down syndrome fibroblasts and mouse Prep1-overexpressing cells display increased sensitivity to genotoxic stress. Nucleic Acids Res 38(11):3595-3604.
5. Kamps MP, Murre C, Sun XH, Baltimore D (1990) A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL. Cell 60(4):547-555.
6. Nourse J, et al. (1990) Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 60(4):535-545.
7. Calvo KR, Knoepfler PS, Sykes DB, Pasillas MP, Kamps MP (2001) Meis1a suppresses differentiation by G-CSF and promotes proliferation by SCF: Potential mechanisms of cooperativity with Hoxa9 in myeloid leukemia. Proc Natl Acad Sci USA 98(23):13120-13125.
8. Longobardi E, et al. (2010) Prep1 (pKnox1)-deficiency leads to spontaneous tumor development in mice and accelerates EmuMyc lymphomagenesis: A tumor suppressor role for Prep1. Mol Oncol 4(2):126-134.
9. Iotti G, et al. (2011) Homeodomain transcription factor and tumor suppressor Prep1 is required to maintain genomic stability. Proc Natl Acad Sci USA 108(29):E314-E322.
10. Massagué J (2008) TGFbeta in Cancer. Cell 134(2):215-230.
11. Heldin C-H, Landström M, Moustakas A (2009) Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Curr Opin Cell Biol 21(2):166-176.
12. Mani SA, et al. (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704-715.
13. Hollier BG, Evans K, Mani SA (2009) The epithelial-to-mesenchymal transition and cancer stem cells: A coalition against cancer therapies. J Mammary Gland Biol Neoplasia 14(1):29-43.
14. Nieto MA (2011) The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu Rev Cell Dev Biol 27:347-376.
15. Keski-Oja J, Blasi F, Leof EB, Moses HL (1988) Regulation of the synthesis and activity of urokinase plasminogen activator in A549 human lung carcinoma cells by transforming growth factor-beta. J Cell Biol 106(2):451-459.
16. Wiercinska E, et al. (2011) The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system. Breast Cancer Res Treat 128(3):657-666.
17. Heldin CH, Moustakas A (2012) Role of Smads in TGFβ signaling. Cell Tissue Res 347(1):21-36.
18. Eferl R, Wagner EF (2003) AP-1: A double-edged sword in tumorigenesis. Nat Rev Cancer 3(11):859-868.
19. Ozanne BW, Spence HJ, McGarry LC, Hennigan RF (2007) Transcription factors control invasion: AP-1 the first among equals. Oncogene 26(1):1-10.
20. Kasai H, Allen JT, Mason RM, Kamimura T, Zhang Z (2005) TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT). Respir Res 6:56.
21. Hua X, Miller ZA, Wu G, Shi Y, Lodish HF (1999) Specificity in transforming growth factor beta-induced transcription of the plasminogen activator inhibitor-1 gene: Interactions of promoter DNA, transcription factor muE3, and Smad proteins. Proc Natl Acad Sci USA 96(23):13130-13135.
22. Conese M, Blasi F (1995) Urokinase/urokinase receptor system: Internalization/degradation of urokinase-serpin complexes: Mechanism and regulation. Biol Chem Hoppe Seyler 376(3):143-155.
23. Sundqvist A, et al. (2013) Specific interactions between Smad proteins and AP-1 components determine TGFβ-induced breast cancer cell invasion. Oncogene 32(31):3606-3615.
24. Longobardi E, Blasi F (2003) Overexpression of PREP-1 in F9 teratocarcinoma cells leads to a functionally relevant increase of PBX-2 by preventing its degradation. J Biol Chem 278(40):39235-39241.
25. Oriente F, et al. (2011) Prep1 controls insulin glucoregulatory function in liver by transcriptional targeting of SHP1 tyrosine phosphatase. Diabetes 60(1):138-147.
26. Oriente F, et al. (2008) Prep1 deficiency induces protection from diabetes and increased insulin sensitivity through a p160-mediated mechanism. Mol Cell Biol 28(18):5634-5645.
27. Dardaei L, Longobardi E, Blasi F (2014) Prep1 and Meis1 competition for Pbx1 binding regulates protein stability and tumorigenesis. Proc Natl Acad Sci USA 111(10):E896-E905.
28. Iotti G, et al. (2012) Reduction of Prep1 levels affects differentiation of normal and malignant B cells and accelerates Myc driven lymphomagenesis. PLoS ONE 7(10):e48353.
29. Berthelsen J, Kilstrup-Nielsen C, Blasi F, Mavilio F, Zappavigna V (1999) The subcellular localization of PBX1 and EXD proteins depends on nuclear import and export signals and is modulated by association with PREP1 and HTH. Genes Dev 13(8):946-953.
30. Penkov D, et al. (2013) Analysis of the DNA-binding profile and function of TALE homeoproteins reveals their specialization and specific interactions with Hox genes/proteins. Cell Reports 3(4):1321-1333.
31. Ficara F, Murphy MJ, Lin M, Cleary ML (2008) Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence. Cell Stem Cell 2(5):484-496.
32. Qiu Y, et al. (2009) Prognostic significance of pre B cell leukemia transcription factor 2 (PBX2) expression in non-small cell lung carcinoma. Cancer Sci 100(7):1198-1209.
33. Consortium EP, et al.; ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414):57-74.
34. Reka AK, et al. (2010) Peroxisome proliferator-activated receptor-gamma activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial-mesenchymal transition. Mol Cancer Ther 9(12):3221-3232.
35. Bailey JS, Rave-Harel N, McGillivray SM, Coss D, Mellon PL (2004) Activin regulation of the follicle-stimulating hormone beta-subunit gene involves Smads and the TALE homeodomain proteins Pbx1 and Prep1. Mol Endocrinol 18(5):1158-1170.
36. Nerlov C, et al. (1992) A regulatory element that mediates co-operation between a PEA3-AP-1 element and an AP-1 site is required for phorbol ester induction of urokinase enhancer activity in HepG2 hepatoma cells. EMBO J 11(12):4573-4582.
37. Berthelsen J, Vandekerkhove J, Blasi F (1996) Purification and characterization of UEF3, a novel factor involved in the regulation of the urokinase and other AP-1 controlled promoters. J Biol Chem 271(7):3822-3830.
38. Verde P, Casalino L, Talotta F, Yaniv M, Weitzman JB (2007) Deciphering AP-1 function in tumorigenesis: Fraternizing on target promoters. Cell Cycle 6(21):2633-2639.
39. Adiseshaiah P, Lindner DJ, Kalvakolanu DV, Reddy SP (2007) FRA-1 proto-oncogene induces lung epithelial cell invasion and anchorage-independent growth in vitro, but is insufficient to promote tumor growth in vivo. Cancer Res 67(13):6204-6211.
40. Caramel J, et al. (2013) A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma. Cancer Cell 24(4):466-480.
41. Desmet CJ, et al. (2013) Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis. Proc Natl Acad Sci USA 110(13):5139-5144.
42. Doehn U, et al. (2009) RSK is a principal effector of the RAS-ERK pathway for eliciting a coordinate promotile/invasive gene program and phenotype in epithelial cells. Mol Cell 35(4):511-522.
43. Shin S, Dimitri CA, Yoon SO, Dowdle W, Blenis J (2010) ERK2 but not ERK1 induces epithelial-to-mesenchymal transformation via DEF motif-dependent signaling events. Mol Cell 38(1):114-127.
44. Zhang Y, Feng XH, Derynck R (1998) Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature 394(6696):909-913.
45. Vincent T, et al. (2009) A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition. Nat Cell Biol 11(8):943-950.
46. Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139(5):871-890.
47. Yang J, Weinberg RA (2008) Epithelial-mesenchymal transition: At the crossroads of development and tumor metastasis. Dev Cell 14(6):818-829.
48. Ferretti E, et al. (2011) A conserved Pbx-Wnt-p63-Irf6 regulatory module controls face morphogenesis by promoting epithelial apoptosis. Dev Cell 21(4):627-641.
49. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119(6):1420-1428.
50. Galvan A, et al. (2013) Gene expression signature of non-involved lung tissue associated with survival in lung adenocarcinoma patients. Carcinogenesis 34(12):2767-2773.