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Cited by 47Wnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene RegulationRenal and related cancers

The Tumor Suppressor PRDM5 Regulates Wnt Signaling at Early Stages of Zebrafish Development

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Meani, Natalia, Pezzimenti, Federica, Deflorian, Gianluca, Mione, Marina, Alcalay, Myriam·2009·PLoS ONE
DOI 10.1371/journal.pone.0004273PMC PMC2627919
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Abstract

PRDM genes are a family of transcriptional regulators that modulate cellular processes such as differentiation, cell growth and apoptosis. Some family members are involved in tissue or organ maturation, and are differentially expressed in specific phases of embryonic development. PRDM5 is a recently identified family member that functions as a transcriptional repressor and behaves as a putative tumor suppressor in different types of cancer. Using gene expression profiling, we found that transcriptional targets of PRDM5 in human U2OS cells include critical genes involved in developmental processes, and specifically in regulating wnt signaling. We therefore assessed PRDM5 function in vivo by performing loss-of-function and gain-of-function experiments in zebrafish embryos. Depletion of prdm5 resulted in impairment of morphogenetic movements during gastrulation and increased the occurrence of the masterblind phenotype in axin+/- embryos, characterized by the loss of eyes and telencephalon. Overexpression of PRDM5 mRNA had opposite effects on the development of anterior neural structures, and resulted in embryos with a shorter body axis due to posterior truncation, a bigger head and abnormal somites. In situ hybridization experiments aimed at analyzing the integrity of wnt pathways during gastrulation at the level of the prechordal plate revealed inhibition of non canonical PCP wnt signaling in embryos overexpressing PRDM5, and over-activation of wnt/beta-catenin signaling in embryos lacking Prdm5. Our data demonstrate that PRDM5 regulates the expression of components of both canonical and non canonical wnt pathways and negatively modulates wnt signaling in vivo.

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  • In zebrafish studies, prdm5 was shown to be essential for convergent extension movements through regulation of Wnt signaling.

    “Its involvement in vertebrate development has been addressed in zebrafish studies; prdm5 was shown to be essential for convergent extension movements through regulation of Wnt signaling [Meani et al., 2009].”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Meani et al., 2009

    The Results section, “prdm5 modulates CE movements during embryogenesis” (page not provided), links prdm5 depletion to disrupted convergent extension movements and altered Wnt signaling. The paper describes prdm5 as modulating these movements, but does not establish that it is essential for them; that word overstates the finding. (LLM, conf=0.82)

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  • The role of PRDM5 does not appear to be limited to ECM development; early studies focused on hypermethylation of the PRDM5 promotor in several types of cancer and its tumor suppressor activity by modulating the Wnt signaling pathway and expression of oncogenes.

    “The role of PRDM5 does not appear to be limited to ECM development.Early studies focused on hypermethylation of the PRDM5 promotor in several types of cancer and its tumor suppressor activity by modulating the Wnt signaling pathway and expression of oncogenes [Watanabe et al., 2007[Watanabe et al., , 2009;;Meani et al., 2009;Cheng et al., 2010].”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Meani et al., 2009

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Research works printed but not linked: 37

  1. [1]Schneider R Bannister AJ Kouzarides T 2002 Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem Sci 27 396 402 12151224
  2. [2]Huang S 2002 Histone methyltransferases, diet nutrients and tumour suppressors. Nat Rev Cancer 2 469 476 12189389
  3. [3]He L Yu JX Liu L Buyse IM Wang MS 1998 RIZ1, but not the alternative RIZ2 product of the same gene, is underexpressed in breast cancer, and forced RIZ1 expression causes G2-M cell cycle arrest and/or apoptosis. Cancer Res 58 4238 4244 9766644
  4. [4]Jiang G Liu L Buyse IM Simon D Huang S 1999 Decreased RIZ1 expression but not RIZ2 in hepatoma and suppression of hepatoma tumorigenicity by RIZ1. Int J Cancer 83 541 546 10508492
  5. [5]Yang XH Huang S 1999 PFM1 (PRDM4), a new member of the PR-domain family, maps to a tumor suppressor locus on human chromosome 12q23-q24.1. Genomics 61 319 325 10552934
  6. [6]Wu Y Ferguson JE 3rd Wang H Kelley R Ren R 2007 PRDM6 is enriched in vascular precursors during development and inhibits endothelial cell proliferation, survival, and differentiation. J Mol Cell Cardiol PMC2683064 17662997
  7. [7]Deng Q Huang S 2004 PRDM5 is silenced in human cancers and has growth suppressive activities. Oncogene 23 4903 4910 15077163
  8. [8]Tam W Gomez M Chadburn A Lee JW Chan WC 2006 Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B-cell lymphomas. Blood 107 4090 4100 16424392
  9. [9]Chadwick RB Jiang GL Bennington GA Yuan B Johnson CK 2000 Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis. Proc Natl Acad Sci U S A 97 2662 2667 10688904 PMC15986
  10. [10]Mitani K Ogawa S Tanaka T Miyoshi H Kurokawa M 1994 Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. EMBO J 13 504 510 8313895 PMC394839
  11. [11]Mochizuki N Shimizu S Nagasawa T Tanaka H Taniwaki M 2000 A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells. Blood 96 3209 3214.12 11050005
  12. [12]Peeters P Wlodarska I Baens M Criel A Selleslag D 1997 Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders. Cancer Res 57 564 569 9044825
  13. [13]Sakurada K Furukawa T Kato Y Kayama T Huang S 2001 RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum. Genes Chromosomes Cancer 30 207 211 11135439
  14. [14]Watanabe Y Toyota M Kondo Y Suzuki H Imai T 2007 PRDM5 identified as a target of epigenetic silencing in colorectal and gastric cancer. Clin Cancer Res 13 4786 4794 17699856
  15. [16]Hoyt PR Bartholomew C Davis AJ Yutzey K Gamer LW 1997 The Evi1 proto-oncogene is required at midgestation for neural, heart, and paraxial mesenchyme development. Mech Dev 65 55 70 9256345
  16. [17]Ohinata Y Payer B O'Carroll D Ancelin K Ono Y 2005 Blimp1 is a critical determinant of the germ cell lineage in mice. Nature 436 207 213 15937476
  17. [18]Wilm TP Solnica-Krezel L 2005 Essential roles of a zebrafish prdm1/blimp1 homolog in embryo patterning and organogenesis. Development 132 393 404 15623803
  18. [19]Finocchiaro G Parise P Minardi SP Alcalay M Muller H 2004 GenePicker: replicate analysis of Affymetrix gene expression microarrays. Bioinformatics 20 3670 3672 15256405
  19. [20]Araki T Milbrandt J 1996 Ninjurin, a novel adhesion molecule, is induced by nerve injury and promotes axonal growth. Neuron 17 353 361 8780658
  20. [21]Poliak S Gollan L Martinez R Custer A Einheber S 1999 Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron 24 1037 1047 10624965
  21. [22]Gibson MA Leavesley DI Ashman LK 1999 Microfibril-associated glycoprotein-2 specifically interacts with a range of bovine and human cell types via alphaVbeta3 integrin. J Biol Chem 274 13060 13065 10224057
  22. [23]Timpl R Sasaki T Kostka G Chu ML 2003 Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol 4 479 489 12778127
  23. [24]Ormestad M Astorga J Landgren H Wang T Johansson BR 2006 Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production. Development 133 833 843 16439479
  24. [25]Porter S Clark IM Kevorkian L Edwards DR 2005 The ADAMTS metalloproteinases. Biochem J 386 15 27 15554875 PMC1134762
  25. [26]Mao B Wu W Davidson G Marhold J Li M 2002 Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature 417 664 667 12050670
  26. [27]Kim KA Zhao J Andarmani S Kakitani M Oshima T 2006 R-Spondin proteins: a novel link to beta-catenin activation. Cell Cycle 5 23 26 16357527
  27. [28]Sinner D Kordich JJ Spence JR Opoka R Rankin S 2007 Sox17 and Sox4 differentially regulate beta-catenin/T-cell factor activity and proliferation of colon carcinoma cells. Mol Cell Biol 27 7802 7815 17875931 PMC2169141
  28. [29]Heisenberg CP Houart C Take-Uchi M Rauch GJ Young N 2001 A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. Genes Dev 15 1427 1434 11390362 PMC312705
  29. [30]Solnica-Krezel L Stemple DL Mountcastle-Shah E Rangini Z Neuhauss SC 1996 Mutations affecting cell fates and cellular rearrangements during gastrulation in zebrafish. Development 123 67 80 9007230
  30. [31]Tada M Smith JC 2000 Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. Development 127 2227 2238 10769246
  31. [32]Cavodeassi F Carreira-Barbosa F Young RM Concha ML Allende ML 2005 Early stages of zebrafish eye formation require the coordinated activity of Wnt11, Fz5, and the Wnt/beta-catenin pathway. Neuron 47 43 56 15996547 PMC2790414
  32. [33]Caneparo L Huang YL Staudt N Tada M Ahrendt R 2007 Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/beta catenin and Wnt/PCP activities, through interaction with the Dally-like homolog Knypek. Genes Dev 21 465 480 17322405 PMC1804334
  33. [34]Larsen M Artym VV Green JA Yamada KM 2006 The matrix reorganized: extracellular matrix remodeling and integrin signaling. Curr Opin Cell Biol 18 463 471 16919434
  34. [35]Song HH Filmus J 2002 The role of glypicans in mammalian development. Biochim Biophys Acta 1573 241 246 12417406
  35. [36]Song HH Shi W Xiang YY Filmus J 2005 The loss of glypican-3 induces alterations in Wnt signaling. J Biol Chem 280 2116 2125 15537637
  36. [37]Clevers H 2006 Wnt/beta-catenin signaling in development and disease. Cell 127 469 480 17081971
  37. [38]Costagli A Kapsimali M Wilson SW Mione M 2002 Conserved and divergent patterns of Reelin expression in the zebrafish central nervous system. J Comp Neurol 450 73 93 12124768

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Authors
Meani, N., Pezzimenti, F., Deflorian, G., Mione, M., & Alcalay, M.
Affiliations
  • European Institute of Oncology (IT)
  • Cogentech S.R.L. Società Benefit a Socio Unico soggetta all’attività di direzione e coordinamento di IFOM - Istituto Fondazione di Oncologia Molecolare ETS (Italy) (IT)
  • IFOM (IT)
  • University of Milan (IT)
Corresponding author
  • Mione, Marina
  • Alcalay, Myriam
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2009-01-26
Volume
4
Issue
1
Pages
e4273
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0004273
PMC
PMC2627919
OpenAlex
W2031383107
Cited by
47
References
1
Citations by year
2026: 1 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 5 · 2014: 1 · 2013: 8 · 2012: 3
FWCI
1.34
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Iris (University of Trento) (submittedVersion)
Funders
  • University College London
  • Fondazione Cariplo
  • Associazione Italiana per la Ricerca sul Cancro
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
Keywords
PRDM5, tumor suppressor, Wnt signaling, zebrafish embryonic development, gastrulation, morphogenetic movements, Axin, canonical Wnt/β-catenin pathway, prechordal plate, somite development, transcriptional repressor, loss of function, gain-of-function
MeSH terms
Animals, DNA-Binding Proteins, Gene Expression Regulation, Humans, Neurons, Phenotype, RNA, Messenger, Transcription Factors, Zebrafish, Signal Transduction, Genes, Tumor Suppressor, In Situ Hybridization, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Tumor Suppressor Proteins, Zebrafish Proteins, Cell Line, Tumor, Wnt Proteins

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