{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC4A7 encodes the electroneutral Na⁺/HCO₃⁻ cotransporter NBCn1, which is emerging as an important mediator of intracellular pH regulation in cancer cells. In the breast, SLC4A7 has been implicated in tumor susceptibility and progression, with several genetic studies linking its locus to breast cancer risk. Elevated NBCn1 expression in primary carcinomas and metastases facilitates increased HCO₃⁻‐dependent acid extrusion, thereby maintaining a more alkaline intracellular pH that supports malignant metabolism, cell survival, and possibly chemoresistance. Moreover, oncogenic signals—such as those from a truncated active HER2 isoform—can post‐transcriptionally upregulate NBCn1 expression, further promoting tumor growth and aggressiveness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cancer, SLC4A7 plays critical roles in normal cellular physiology. In vascular smooth muscle and endothelial cells, genotype‐dependent differences in NBCn1 expression influence intracellular pH regulation and are linked to blood pressure regulation. In macrophages, SLC4A7 is strongly induced during differentiation and is essential for proper phagosome acidification, a key step in pathogen clearance, by buffering pH changes during active phagocytosis. In addition, recent evidence indicates that mTORC1 signaling enhances the translation of SLC4A7, thereby harnessing extracellular bicarbonate to drive de novo nucleotide synthesis and cell growth."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, structural and regulatory insights have begun to clarify how SLC4A7/NBCn1 activity is controlled. Detailed analyses reveal that specific extracellular and transmembrane domains of NBCn1 determine its electroneutral transport character and proper plasma membrane targeting. Protein–protein interactions—for example with scaffolding proteins or enzymes like carbonic anhydrase II—may further modulate its activity, while post‐transcriptional mechanisms mediated by its 3′ untranslated region contribute to the fine‐tuning of transporter expression. 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