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July 3rd, 2025
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Kent State University
cancer biology
biorxiv

Cell Settling, Migration, and Stochastic Cancer Expression Suggest Potassium Flux Per H+- Sensitive KCN Members Associated with Oncogenes and Histone/DNA Modulators Potentially Initiates pH-Reversal

Beckner, M.Open in Google Scholar

Attraction of glioblastoma cells to potassium was suspected when cells clustered around dying cells and they migrated towards serum (high [K+]) and a positive potassium gradient. Potassium channel proteins (KCN family, 90 members) mediating altered transmembrane flux may provide K+ that releases H+ bound to inner membranes in cancer cells for cytosolic proton transfer (possibly Grotthuss) to extrusion sites. Cell settling and migration assay results led to collection of 70 studies, unbiased by authors for inclusion of KCN genes, that detected KCN differentially expressed genes (DEG). Of 53 KCN DEG found among 29 malignancies, 62.3% encoded H+-sensitive proteins. KCN DEG encoding H+-sensitive proteins were more prevalent in 50 studies involving one or more of 8 categories (7 oncogenes and histone/DNA modifiers) versus those with none, p = 0.0325. Pertinent genes for lactate outflow, etc. had relatively normal expressions. Brain tumors in REMBRANDT (database) showed altered expression of KCN genes encoding H+-sensitive proteins in glioblastomas versus less invasive oligodendrogliomas of patients on anti-seizure medications, with less KCNJ16 /Kir5.1, p = 5.32 x 10-8. Altered H+-sensitive potassium flux via the KCN family downstream of oncogenes and histone/DNA modifiers putatively incites proton transfers for H+ release during pH reversal in cancer.

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