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Overexpression of Na V 1.6 channels is associated with the invasion capacity of human cervical cancer
Author(s) -
HernandezPlata Everardo,
Ortiz Cindy S.,
MarquinaCastillo Brenda,
MedinaMartinez Ingrid,
Alfaro Ana,
Berumen Jaime,
Rivera Manuel,
Gomora Juan C.
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26210
Subject(s) - cervical cancer , cancer , cancer research , medicine , biology
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 Na V 1.6 α‐subunit in CaC samples were ∼40‐fold higher than in noncancerous cervical (NCC) biopsies. A Na V 1.7 α‐subunit variant also showed increased mRNA levels in CaC (∼20‐fold). All four Na V β subunits were also detected in CaC samples, being Na V β1 the most abundant. Proteins of Na V 1.6 and Na V 1.7 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 Na V 1.6 channels in the plasma membrane of CaC cells was confirmed by whole‐cell patch‐clamp experiments using Cn2, a Na V 1.6‐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 Na V 1.6 is upregulated in CaC and could serve as a novel molecular marker for the metastatic behavior of this carcinoma.