
Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)
Опубликована: Март 27, 2025
Oncogenes drive cancer progression, but few are active exclusively in tumor cells. Connexins (Cxs), traditionally recognized as ion channel proteins, can localize to the nucleus and regulate gene expression, playing key roles both physiological pathological processes. Cx46, once thought be restricted eye lens, has been implicated growth, though its underlying mechanisms remain unclear. This study investigates nuclear presence of Cx46 cells potential role a transcriptional modulator. We employed ChIP-Seq, confocal immunofluorescence, protein purification assess localization DNA interactions. Functional assays were conducted evaluate effects on invasion, division, spheroid formation, mesenchymal marker expression. Single-point mutations molecular dynamics simulations used explore Cx46-DNA mRNA upregulation was found variety tumors compared adjacent healthy tissue. In HeLa cells, which do not express transfection promoted proliferation, invasion self-renewal capacity, stem cell traits features. Consistently, Sk-Mel-2, naturally reduced expression led decrease similar parameters. detected two forms, full length 46 kDa 30 fragment (GJA3-30 k), ChIP-Seq experiments revealed that binds at intergenic promoter regions, leading activation oncogenic pathways. Molecular suggest GJA3-30 k dimerizes RAD50-like structure, forming stable complexes. some cases nuclei multiple lines, including prostate, breast skin cancers. Our findings reveal novel for cancer, demonstrating function regulator therapeutic target.
Язык: Английский