The invasiveness of human cervical cancer associated to the function of NaV 1.6 channels is mediated by MMP-2 activity

Scientific Reports
Osbaldo Lopez-CharcasJuan C Gomora

Abstract

Voltage-gated sodium (NaV) channels have been related with cell migration and invasiveness in human cancers. We previously reported the contribution of NaV1.6 channels activity with the invasion capacity of cervical cancer (CeCa) positive to Human Papilloma Virus type 16 (HPV16), which accounts for 50% of all CeCa cases. Here, we show that NaV1.6 gene (SCN8A) overexpression is a general characteristic of CeCa, regardless of the HPV type. In contrast, no differences were observed in NaV1.6 channel expression between samples of non-cancerous and cervical intraepithelial neoplasia. Additionally, we found that CeCa cell lines, C33A, SiHa, CaSki and HeLa, express mainly the splice variant of SCN8A that lacks exon 18, shown to encode for an intracellularly localized NaV1.6 channel, whereas the full-length adult form was present in CeCa biopsies. Correlatively, patch-clamp experiments showed no evidence of whole-cell sodium currents (INa) in CeCa cell lines. Heterologous expression of full-length NaV1.6 isoform in C33A cells produced INa, which were sufficient to significantly increase invasion capacity and matrix metalloproteinase type 2 (MMP-2) activity. These data suggest that upregulation of NaV1.6 channel expression occurs when c...Continue Reading

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Citations

Mar 22, 2019·Frontiers in Oncology·Weijia MaoSongcheng Ying
Mar 1, 2019·Cancer Cell International·Ana Laura Sanchez-Sandoval, Juan Carlos Gomora
Aug 10, 2020·Scientific Reports·Lucile PoissonDriffa Moussata
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Jul 14, 2020·Frontiers in Pharmacology·Alexis Díaz-García, Diego Varela
Feb 6, 2021·Drug Discovery Today·Jesse HorneYuping Bao
Dec 3, 2021·Molecular and Cellular Biochemistry·Salman AhmedWai San Cheang

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Datasets Mentioned

BETA
GM6001
GTX80928
GTX122148

Methods Mentioned

BETA
biopsies
PCR
confocal microscopy
electrophoresis
transfections
hysterectomy
biopsy
Assay
Protein Assay
X-ray

Software Mentioned

GraphPad Prism
Elements Advanced Research Imaging
Fiji
Gel Tool
SPSS
pCLAMP
NIS

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