PMID- 29967069
OWN - NLM
STAT- MEDLINE
DCOM- 20190318
LR  - 20240402
IS  - 1754-8411 (Electronic)
IS  - 1754-8403 (Print)
IS  - 1754-8403 (Linking)
VI  - 11
IP  - 9
DP  - 2018 Aug 16
TI  - A carcinogenic trigger to study the function of tumor suppressor genes in 
      Schmidtea mediterranea.
LID - 10.1242/dmm.032573 [doi]
LID - dmm032573
AB  - Planarians have been long known for their regenerative ability, which hinges on 
      pluripotency. Recently, however, the planarian model has been successfully 
      established for routine toxicological screens aimed to assess overproliferation, 
      mutagenicity and tumorigenesis. In this study, we focused on planarian tumor 
      suppressor genes (TSGs) and their role during chemically induced carcinogenic 
      stress in Schmidtea mediterranea Combining in silico and proteomic screens with 
      exposure to human carcinogen type 1A agent cadmium (Cd), we showed that many TSGs 
      have a function in stem cells and that, in general, exposure to Cd accelerated 
      the onset and increased the severity of the observed phenotype. This suggested 
      that the interaction between environmental and genetic factors plays an important 
      role in tumor development in S. mediterranea Therefore, we further focused on the 
      synergistic effects of Cd exposure and p53 knockdown (KD) at the cellular and 
      molecular levels. Cd also produced a specific proteomic landscape in homeostatic 
      animals, with 172 proteins differentially expressed, 43 of which were 
      downregulated. Several of these proteins have tumor suppressor function in human 
      and other animals, namely Wilms Tumor 1 Associated Protein (WT1), Heat Shock 
      Protein 90 (HSP90), Glioma Pathogenesis-Related Protein 1 (GLIPR1) and Matrix 
      Metalloproteinase B (Smed-MMPB). Both Glipr1 and MmpB KD produced large 
      outgrowths, epidermal lesions and epidermal blisters. The epidermal blisters that 
      formed as a consequence of Smed-MmpB KD were populated by smedwi1(+) cells, many 
      of which were actively proliferating, while large outgrowths contained 
      ectopically differentiated structures, such as photoreceptors, nervous tissue and 
      a small pharynx. In conclusion, Smed-MmpB is a planarian TSG that prevents stem 
      cell proliferation and differentiation outside the proper milieu.
CI  - (c) 2018. Published by The Company of Biologists Ltd.
FAU - Van Roten, Andromeda
AU  - Van Roten A
AUID- ORCID: 0000-0002-6047-1141
AD  - Zoology: Biodiversity and Toxicology, Hasselt University-Campus Diepenbeek, 
      Agoralaan 1, Gebouw D, 3590, Diepenbeek, Belgium.
FAU - Barakat, Amal Zohir Abo-Zeid
AU  - Barakat AZA
AUID- ORCID: 0000-0002-7824-4094
AD  - Planarian Stem Cell Laboratory, Max Planck Institute for Molecular Biomedicine, 
      von Esmarch-str. 54, 48149, Munster, Germany.
FAU - Wouters, Annelies
AU  - Wouters A
AUID- ORCID: 0000-0001-6691-2713
AD  - Zoology: Biodiversity and Toxicology, Hasselt University-Campus Diepenbeek, 
      Agoralaan 1, Gebouw D, 3590 Diepenbeek, Belgium.
FAU - Tran, Thao Anh
AU  - Tran TA
AUID- ORCID: 0000-0003-2948-9391
AD  - Pluripotency and Regeneration Group, Fraunhofer Institute for Biomedical 
      Engineering, Joseph-von-Fraunhofer-Weg 1, 66280, Sulzbach, Germany.
FAU - Mouton, Stijn
AU  - Mouton S
AUID- ORCID: 0000-0002-1123-6268
AD  - European Research Institute for the Biology of Ageing, University Medical Center 
      Groningen, University of Groningen, 9713, Groningen, The Netherlands.
FAU - Noben, Jean-Paul
AU  - Noben JP
AUID- ORCID: 0000-0003-3368-5686
AD  - Biomedical Research Institute, Hasselt University and Transnationale Universiteit 
      Limburg, School of Life Sciences, 3590, Diepenbeek, Belgium.
FAU - Gentile, Luca
AU  - Gentile L
AUID- ORCID: 0000-0002-7393-7502
AD  - Planarian Stem Cell Laboratory, Max Planck Institute for Molecular Biomedicine, 
      von Esmarch-str. 54, 48149, Munster, Germany mckind75@gmail.com.
FAU - Smeets, Karen
AU  - Smeets K
AD  - Zoology: Biodiversity and Toxicology, Hasselt University-Campus Diepenbeek, 
      Agoralaan 1, Gebouw D, 3590, Diepenbeek, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180816
PL  - England
TA  - Dis Model Mech
JT  - Disease models & mechanisms
JID - 101483332
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 00BH33GNGH (Cadmium)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Cadmium/toxicity
MH  - Carcinogenesis/drug effects/*genetics
MH  - Cell Proliferation
MH  - Epidermis/pathology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Knockdown Techniques
MH  - *Genes, Tumor Suppressor
MH  - Homeostasis
MH  - Oxidative Stress/drug effects
MH  - Phenotype
MH  - Planarians/*genetics
MH  - Proteomics
MH  - RNA Interference
MH  - Stem Cells/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
PMC - PMC6176991
OTO - NOTNLM
OT  - Cadmium
OT  - Carcinogens
OT  - Matrix-metalloproteinases
OT  - Planarian
OT  - Stem cells
OT  - Tumor suppressor genes
COIS- Competing interestsThe authors declare no competing or financial interests.
EDAT- 2018/07/04 06:00
MHDA- 2019/03/19 06:00
PMCR- 2018/08/16
CRDT- 2018/07/04 06:00
PHST- 2017/11/12 00:00 [received]
PHST- 2018/06/25 00:00 [accepted]
PHST- 2018/07/04 06:00 [pubmed]
PHST- 2019/03/19 06:00 [medline]
PHST- 2018/07/04 06:00 [entrez]
PHST- 2018/08/16 00:00 [pmc-release]
AID - dmm.032573 [pii]
AID - DMM032573 [pii]
AID - 10.1242/dmm.032573 [doi]
PST - epublish
SO  - Dis Model Mech. 2018 Aug 16;11(9):dmm032573. doi: 10.1242/dmm.032573.