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Overexpression of NaV1.6 channels is associated with the invasion capacity of human cervical cancer

Functional activity of voltage‐gated sodium channels (VGSC) has been associated to the invasion and metastasis behaviors of prostate, breast and some other types of cancer. We previously reported the functional expression of VGSC in primary cultures and biopsies derived from cervical cancer (CaC). H...

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Published in:International journal of cancer 2012-05, Vol.130 (9), p.2013-2023
Main Authors: Hernandez-Plata, Everardo, Ortiz, Cindy S., Marquina-Castillo, Brenda, Medina-Martinez, Ingrid, Alfaro, Ana, Berumen, Jaime, Rivera, Manuel, Gomora, Juan C.
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container_end_page 2023
container_issue 9
container_start_page 2013
container_title International journal of cancer
container_volume 130
creator Hernandez-Plata, Everardo
Ortiz, Cindy S.
Marquina-Castillo, Brenda
Medina-Martinez, Ingrid
Alfaro, Ana
Berumen, Jaime
Rivera, Manuel
Gomora, Juan C.
description Functional activity of voltage‐gated sodium channels (VGSC) has been associated to the invasion and metastasis behaviors of prostate, breast and some other types of cancer. We previously reported the functional expression of VGSC in primary cultures and biopsies derived from cervical cancer (CaC). Here, we investigate the relative expression levels of VGSC subunits and its possible role in CaC. Quantitative real‐time PCR revealed that mRNA levels of NaV1.6 α‐subunit in CaC samples were ∼40‐fold higher than in noncancerous cervical (NCC) biopsies. A NaV1.7 α‐subunit variant also showed increased mRNA levels in CaC (∼20‐fold). All four NaVβ subunits were also detected in CaC samples, being NaVβ1 the most abundant. Proteins of NaV1.6 and NaV1.7 α‐subunits were immunolocalized in both NCC and CaC biopsies and in CaC primary cultures as well; however, although in NCC sections proteins were mainly relegated to the plasma membrane, in CaC biopsies and primary cultures the respective signal was stronger and widely distributed in both cytoplasm and plasma membrane. Functional activity of NaV1.6 channels in the plasma membrane of CaC cells was confirmed by whole‐cell patch‐clamp experiments using Cn2, a NaV1.6‐specific toxin, which blocked ∼30% of the total sodium current. Blocking of sodium channels VGSC with tetrodotoxin and Cn2 did not affect proliferation neither migration, but reduced by ∼20% the invasiveness of CaC primary culture cells in vitro assays. We conclude that NaV1.6 is upregulated in CaC and could serve as a novel molecular marker for the metastatic behavior of this carcinoma.
doi_str_mv 10.1002/ijc.26210
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J. Cancer</addtitle><description>Functional activity of voltage‐gated sodium channels (VGSC) has been associated to the invasion and metastasis behaviors of prostate, breast and some other types of cancer. We previously reported the functional expression of VGSC in primary cultures and biopsies derived from cervical cancer (CaC). Here, we investigate the relative expression levels of VGSC subunits and its possible role in CaC. Quantitative real‐time PCR revealed that mRNA levels of NaV1.6 α‐subunit in CaC samples were ∼40‐fold higher than in noncancerous cervical (NCC) biopsies. A NaV1.7 α‐subunit variant also showed increased mRNA levels in CaC (∼20‐fold). All four NaVβ subunits were also detected in CaC samples, being NaVβ1 the most abundant. 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subjects Behavior
Biological and medical sciences
Biopsy
Cancer
Cervical cancer
Female genital diseases
Gynecology. Andrology. Obstetrics
invasiveness
Medical research
Medical sciences
molecular marker
NaV1.6
NaV1.7
Rodents
Tumors
title Overexpression of NaV1.6 channels is associated with the invasion capacity of human cervical cancer
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