PMID- 36293469
OWN - NLM
STAT- MEDLINE
DCOM- 20221028
LR  - 20221030
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 20
DP  - 2022 Oct 20
TI  - ADAM10 and ADAM17-Novel Players in Retinoblastoma Carcinogenesis.
LID - 10.3390/ijms232012621 [doi]
LID - 12621
AB  - A disintegrin and metalloproteinase (ADAM) family proteins, acting as sheddases, 
      are important factors in a number of pathologies, including cancer, and have been 
      suggested as promising therapeutic targets. The study presented focuses on the 
      involvement of ADAM10 and ADAM17 in retinoblastoma (RB), the most common 
      malignant intraocular childhood tumor. A significant correlation between ADAM17 
      expression levels and RB laterality and RB staging was observed. Levels of ADAM10 
      or ADAM17 regulating miRNAs miR-145, -152, and -365 were significantly 
      downregulated in RB cell lines, and reduced miR levels with simultaneously 
      upregulated ADAM10 and ADAM17 expression were found in RB patients. The 
      involvement of both ADAMs analyzed in ectodomain shedding of the neuronal cell 
      adhesion molecule L1 (L1CAM), shown to induce pro-tumorigenic effects in RB, was 
      confirmed. Lentiviral ADAM10 and ADAM17 single or ADAM10/17 double knockdown (KD) 
      induced caspase-dependent apoptosis and reduced cell viability, proliferation, 
      growth, and colony formation capacity of RB cells. Moreover, differential 
      phosphorylation of the serine/threonine kinase AKT was observed following ADAM17 
      KD in RB cells. Chicken chorioallantoic membrane (CAM) assays revealed that 
      ADAM17 and ADAM10/17 depletion decreases the tumorigenic and migration potential 
      of RB cells in vivo. Thus, ADAMs are potential novel targets for future 
      therapeutic RB approaches.
FAU - Van Meenen, Dario
AU  - Van Meenen D
AUID- ORCID: 0000-0003-1412-1017
AD  - Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Institute of 
      Anatomy II, Department of Neuroanatomy, Medical Faculty, University of 
      Duisburg-Essen, 45147 Essen, Germany.
FAU - Doege, Annika
AU  - Doege A
AD  - Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Institute of 
      Anatomy II, Department of Neuroanatomy, Medical Faculty, University of 
      Duisburg-Essen, 45147 Essen, Germany.
FAU - Alefeld, Emily
AU  - Alefeld E
AD  - Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Institute of 
      Anatomy II, Department of Neuroanatomy, Medical Faculty, University of 
      Duisburg-Essen, 45147 Essen, Germany.
FAU - Haase, Andre
AU  - Haase A
AUID- ORCID: 0000-0002-4529-1396
AD  - Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Institute of 
      Anatomy II, Department of Neuroanatomy, Medical Faculty, University of 
      Duisburg-Essen, 45147 Essen, Germany.
FAU - Beier, Manfred
AU  - Beier M
AD  - Institute of Human Genetics, Medical Faculty, Heinrich-Heine University 
      Dusseldorf, 40225 Dusseldorf, Germany.
FAU - Kiefer, Tobias
AU  - Kiefer T
AD  - Department of Ophthalmology, Medical Faculty, University of Duisburg-Essen, 45147 
      Essen, Germany.
FAU - Biewald, Eva
AU  - Biewald E
AD  - Department of Ophthalmology, Medical Faculty, University of Duisburg-Essen, 45147 
      Essen, Germany.
FAU - Metz, Klaus
AU  - Metz K
AD  - Institute of Pathology, Medical Faculty, University of Duisburg-Essen, 45147 
      Essen, Germany.
FAU - Drager, Oliver
AU  - Drager O
AD  - Institute of Cellular Neurophysiology, Medical Faculty, University of Bielefeld, 
      33615 Bielefeld, Germany.
FAU - Busch, Maike Anna
AU  - Busch MA
AUID- ORCID: 0000-0001-9651-031X
AD  - Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Institute of 
      Anatomy II, Department of Neuroanatomy, Medical Faculty, University of 
      Duisburg-Essen, 45147 Essen, Germany.
FAU - Dunker, Nicole
AU  - Dunker N
AUID- ORCID: 0000-0003-1273-0644
AD  - Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Institute of 
      Anatomy II, Department of Neuroanatomy, Medical Faculty, University of 
      Duisburg-Essen, 45147 Essen, Germany.
LA  - eng
GR  - no excisting grant number/ELAN Promotionskolleg and Stiftung Universitatsmedizin 
      Essen./
PT  - Journal Article
DEP - 20221020
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Disintegrins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Neural Cell Adhesion Molecule L1)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - 0 (Membrane Proteins)
RN  - EC 3.4.24.81 (ADAM10 Protein)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - 0 (MicroRNAs)
RN  - 452VLY9402 (Serine)
RN  - EC 3.4.24.81 (ADAM10 protein, human)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
RN  - 0 (MIRN145 microRNA, human)
SB  - IM
MH  - Humans
MH  - Disintegrins
MH  - *Retinoblastoma/genetics
MH  - Proto-Oncogene Proteins c-akt
MH  - *Neural Cell Adhesion Molecule L1
MH  - Amyloid Precursor Protein Secretases/genetics/metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - ADAM10 Protein/genetics/metabolism
MH  - ADAM17 Protein/genetics/metabolism
MH  - *MicroRNAs/genetics
MH  - Carcinogenesis/genetics
MH  - *Retinal Neoplasms
MH  - Serine
PMC - PMC9604041
OTO - NOTNLM
OT  - ADAM10
OT  - ADAM17
OT  - CAM assay
OT  - L1CAM
OT  - carcinogenesis
OT  - retinoblastoma
OT  - tumorigenesis
COIS- The authors declare no conflict of interest.
EDAT- 2022/10/28 06:00
MHDA- 2022/10/29 06:00
PMCR- 2022/10/20
CRDT- 2022/10/27 01:24
PHST- 2022/08/31 00:00 [received]
PHST- 2022/10/12 00:00 [revised]
PHST- 2022/10/18 00:00 [accepted]
PHST- 2022/10/27 01:24 [entrez]
PHST- 2022/10/28 06:00 [pubmed]
PHST- 2022/10/29 06:00 [medline]
PHST- 2022/10/20 00:00 [pmc-release]
AID - ijms232012621 [pii]
AID - ijms-23-12621 [pii]
AID - 10.3390/ijms232012621 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Oct 20;23(20):12621. doi: 10.3390/ijms232012621.