PMID- 36768862
OWN - NLM
STAT- MEDLINE
DCOM- 20230214
LR  - 20230214
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 3
DP  - 2023 Jan 28
TI  - NMDA Receptor and Its Emerging Role in Cancer.
LID - 10.3390/ijms24032540 [doi]
LID - 2540
AB  - Glutamate is a key player in excitatory neurotransmission in the central nervous 
      system (CNS). The N-methyl-D-aspartate receptor (NMDAR) is a glutamate-gated ion 
      channel which presents several unique features and is involved in various 
      physiological and pathological neuronal processes. Thanks to great efforts in 
      neuroscience, its structure and the molecular mechanisms controlling its 
      localization and functional regulation in neuronal cells are well known. The 
      signaling mediated by NMDAR in neurons is very complex as it depends on its 
      localization, composition, Ca(2+) influx, and ion flow-independent conformational 
      changes. Moreover, NMDA receptors are highly diffusive in the plasma membrane of 
      neurons, where they form heterocomplexes with other membrane receptors and 
      scaffold proteins which determine the receptor function and activation of 
      downstream signaling. Interestingly, a recent paper demonstrates that NMDAR 
      signaling is involved in epithelial cell competition, an evolutionary conserved 
      cell fitness process influencing cancer initiation and progress. The idea that 
      NMDAR signaling is limited to CNS has been challenged in the past two decades. A 
      large body of evidence suggests that NMDAR is expressed in cancer cells outside 
      the CNS and can respond to the autocrine/paracrine release of glutamate. In this 
      review, we survey research on NMDAR signaling and regulation in neurons that can 
      help illuminate its role in tumor biology. Finally, we will discuss existing data 
      on the role of the glutamine/glutamate metabolism, the anticancer action of NMDAR 
      antagonists in experimental models, NMDAR synaptic signaling in tumors, and 
      clinical evidence in human cancer.
FAU - Gallo, Simona
AU  - Gallo S
AUID- ORCID: 0000-0001-7404-1356
AD  - Department of Oncology, University of Turin, Strada Provinciale 142, 10060 
      Candiolo, Italy.
AD  - Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142, 10060 Candiolo, 
      Italy.
FAU - Vitacolonna, Annapia
AU  - Vitacolonna A
AUID- ORCID: 0000-0002-7492-6100
AD  - Department of Oncology, University of Turin, Strada Provinciale 142, 10060 
      Candiolo, Italy.
AD  - Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142, 10060 Candiolo, 
      Italy.
FAU - Crepaldi, Tiziana
AU  - Crepaldi T
AUID- ORCID: 0000-0003-3410-947X
AD  - Department of Oncology, University of Turin, Strada Provinciale 142, 10060 
      Candiolo, Italy.
AD  - Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142, 10060 Candiolo, 
      Italy.
LA  - eng
GR  - CRT 2021.1899/Fondazione CRT/
GR  - Ricerca corrente 2022/Ministero della Salute/
PT  - Journal Article
PT  - Review
DEP - 20230128
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Humans
MH  - *Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Signal Transduction/physiology
MH  - Synaptic Transmission
MH  - *Neoplasms
MH  - Glutamic Acid/metabolism
PMC - PMC9917092
OTO - NOTNLM
OT  - NMDAR
OT  - cancers
OT  - glutamate
OT  - metabolism
OT  - neuron
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/12 06:00
MHDA- 2023/02/15 06:00
PMCR- 2023/01/28
CRDT- 2023/02/11 01:22
PHST- 2022/12/23 00:00 [received]
PHST- 2023/01/23 00:00 [revised]
PHST- 2023/01/25 00:00 [accepted]
PHST- 2023/02/11 01:22 [entrez]
PHST- 2023/02/12 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
PHST- 2023/01/28 00:00 [pmc-release]
AID - ijms24032540 [pii]
AID - ijms-24-02540 [pii]
AID - 10.3390/ijms24032540 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jan 28;24(3):2540. doi: 10.3390/ijms24032540.