PMID- 38201232
OWN - NLM
STAT- MEDLINE
DCOM- 20240112
LR  - 20240201
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Dec 21
TI  - MET Oncogene Enhances Pro-Migratory Functions by Counteracting NMDAR2B Cleavage.
LID - 10.3390/cells13010028 [doi]
LID - 28
AB  - The involvement of the N-methyl-D-aspartate receptor (NMDAR), a glutamate-gated 
      ion channel, in promoting the invasive growth of cancer cells is an area of 
      ongoing investigation. Our previous findings revealed a physical interaction 
      between NMDAR and MET, the hepatocyte growth factor (HGF) receptor. However, the 
      molecular mechanisms underlying this NMDAR/MET interaction remain unclear. In 
      this study, we demonstrate that the NMDAR2B subunit undergoes proteolytic 
      processing, resulting in a low-molecular-weight form of 100 kDa. Interestingly, 
      when the NMDAR2B and MET constructs were co-transfected, the full-size 
      high-molecular-weight NMDAR2B form of 160 kDa was predominantly observed. The 
      protection of NMDAR2B from cleavage was dependent on the kinase activity of MET. 
      We provide the following evidence that MET opposes the autophagic lysosomal 
      proteolysis of NMDAR2B: (i) MET decreased the protein levels of lysosomal 
      cathepsins; (ii) treatment with either an inhibitor of autophagosome formation or 
      the fusion of the autophagosome and lysosome elevated the proportion of the 
      NMDAR2B protein's uncleaved form; (iii) a specific mTOR inhibitor hindered the 
      anti-autophagic effect of MET. Finally, we demonstrate that MET coopts NMDAR2B to 
      augment cell migration. This implies that MET harnesses the functionality of 
      NMDAR2B to enhance the ability of cancer cells to migrate.
FAU - Gallo, Simona
AU  - Gallo S
AUID- ORCID: 0000-0001-7404-1356
AD  - Department of Oncology, University of Turin, Regione Gonzole 10, 10143 Orbassano, 
      Italy.
AD  - Candiolo Cancer Institute, FPO-IRCCS, SP142, Km 3.95, 10060 Candiolo, Italy.
FAU - Vitacolonna, Annapia
AU  - Vitacolonna A
AUID- ORCID: 0000-0002-7492-6100
AD  - Department of Oncology, University of Turin, Regione Gonzole 10, 10143 Orbassano, 
      Italy.
AD  - Candiolo Cancer Institute, FPO-IRCCS, SP142, Km 3.95, 10060 Candiolo, Italy.
FAU - Comoglio, Paolo Maria
AU  - Comoglio PM
AUID- ORCID: 0000-0003-4971-3987
AD  - IFOM ETS-The AIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milano, 
      Italy.
FAU - Crepaldi, Tiziana
AU  - Crepaldi T
AUID- ORCID: 0000-0003-3410-947X
AD  - Department of Oncology, University of Turin, Regione Gonzole 10, 10143 Orbassano, 
      Italy.
AD  - Candiolo Cancer Institute, FPO-IRCCS, SP142, Km 3.95, 10060 Candiolo, Italy.
LA  - eng
GR  - 21052/Italian Association for Cancer Research/
GR  - 23820/Italian Association for Cancer Research/
GR  - Ricerca corrente 2023/Ministero della Salute/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231221
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - *Receptors, N-Methyl-D-Aspartate
MH  - *Autophagosomes
MH  - Autophagy
MH  - Glutamic Acid
MH  - Oncogenes
PMC - PMC10777984
OTO - NOTNLM
OT  - MET tyrosine kinase receptor
OT  - NMDAR
OT  - cancers
OT  - cell migration
OT  - glutamate receptor
OT  - proteolytic cleavage
COIS- The authors declare no conflict of interest.
EDAT- 2024/01/11 07:43
MHDA- 2024/01/12 06:42
PMCR- 2023/12/21
CRDT- 2024/01/11 01:04
PHST- 2023/11/22 00:00 [received]
PHST- 2023/12/19 00:00 [accepted]
PHST- 2024/01/12 06:42 [medline]
PHST- 2024/01/11 07:43 [pubmed]
PHST- 2024/01/11 01:04 [entrez]
PHST- 2023/12/21 00:00 [pmc-release]
AID - cells13010028 [pii]
AID - cells-13-00028 [pii]
AID - 10.3390/cells13010028 [doi]
PST - epublish
SO  - Cells. 2023 Dec 21;13(1):28. doi: 10.3390/cells13010028.