PMID- 34471818
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210903
IS  - 2576-3113 (Electronic)
IS  - 2576-3105 (Print)
IS  - 2576-3105 (Linking)
VI  - 1
IP  - 3
DP  - 2019 Sep 1
TI  - Effect of Sigma-1 Receptors on Voltage-Gated Sodium Ion Channels in Colon Cancer 
      Cell Line SW620.
PG  - 158-168
LID - 10.1089/bioe.2019.0015 [doi]
AB  - Background: Voltage-gated sodium channels (VGSCs) play pivotal roles in the 
      metastatic process in several cancers, including breast and colon cancers. 
      Sigma-1 receptors are known to interact and form complexes with a number of ion 
      channels aiding the delivery of the channel protein to the plasma membrane. Drugs 
      that bind the Sigma-1 receptor are hypothesized to affect this process and reduce 
      the delivery of the channel protein to the plasma membrane, in turn reducing the 
      metastatic potential of the cells. Methods: Human colon cancer cell line SW620 
      was utilized as a model to investigate the interaction between the neonatal VGSC 
      (nNav1.5) and the Sigma-1 receptor. This was accomplished using drugs that bind 
      the Sigma-1 receptor, Sigma-1 receptor silencing, and antibodies that bind and 
      block the nNav1.5 channel. Results: Sigma-1 receptor drugs SKF10047 and dimethyl 
      tryptamine were found to alter (reduce) the adhesion of these cells by 46-54% at 
      a 20 muM drug concentration. In a similar manner, gene silencing of the Sigma-1 
      receptor had a similar effect in reducing the adhesion of these cells to 
      collagen-coated plates by 30%. The Sigma-1 receptor was found to be in a complex 
      with nNav1.5 in SW620 cells, and Sigma-1 drugs or gene silencing of the Sigma-1 
      receptor results in a reduction of the surface expression of nNav1.5 by  approximately 50%. 
      Culture of SW620 cells under hypoxic conditions resulted in upregulation of the 
      Sigma-1 receptor and nNav1.5. In addition, surface expression of nNav1.5 protein 
      increased under hypoxic culture conditions and this was inhibited by the 
      application of SKF10047. Conclusions: It is proposed that in colon cancer cells, 
      upregulated Sigma-1 receptor expression in hypoxia led to increased nNav1.5 
      protein expression at the plasma membrane and resulted in the cells switching to 
      a more invasive state.
CI  - Copyright 2019, Mary Ann Liebert, Inc., publishers.
FAU - Aydar, Ebru
AU  - Aydar E
AD  - Institute of Ophthalmology, University College London, London, United Kingdom.
FAU - Palmer, Christopher
AU  - Palmer C
AD  - School of Health Sciences, London Metropolitan University, London, United 
      Kingdom.
LA  - eng
PT  - Journal Article
DEP - 20190916
PL  - United States
TA  - Bioelectricity
JT  - Bioelectricity
JID - 101747121
PMC - PMC8370282
OTO - NOTNLM
OT  - Sigma-1 receptor
OT  - colon cancer
OT  - sodium channel
COIS- No competing financial interests exist.
EDAT- 2019/09/01 00:00
MHDA- 2019/09/01 00:01
PMCR- 2020/09/01
CRDT- 2021/09/02 07:00
PHST- 2021/09/02 07:00 [entrez]
PHST- 2019/09/01 00:00 [pubmed]
PHST- 2019/09/01 00:01 [medline]
PHST- 2020/09/01 00:00 [pmc-release]
AID - 10.1089/bioe.2019.0015 [pii]
AID - 10.1089/bioe.2019.0015 [doi]
PST - ppublish
SO  - Bioelectricity. 2019 Sep 1;1(3):158-168. doi: 10.1089/bioe.2019.0015. Epub 2019 
      Sep 16.