NHE3 (Sodium/Hydrogen Exchanger 3), encoded by the SLC9A3 gene, is best known for its role in maintaining sodium and fluid balance as well as intracellular pH, particularly in epithelial tissues such as the intestine and kidney.
-well known that NHE3 activity is increased with PI3K cascade activation
• NHE3 is central to regulating the intracellular pH by exchanging intracellular H⁺ for extracellular Na⁺.
• By controlling pH and ion balance, NHE3 indirectly contributes to cell volume regulation, nutrient absorption, and overall epithelial barrier integrity.
• In non-transformed tissues, NHE3 activity supports normal metabolic functions and cellular homeostasis.
Expression in Cancer
• Tumor Microenvironment: Cancer cells often face an acidic microenvironment; alterations in NHE activity (including NHE3) could help tumor cells adapt by regulating intracellular pH.
-The degree of NHE3 expression (upregulation or downregulation) may vary with cancer type and the specific tumor microenvironment, influencing local pH balance and, consequently, tumor behavior.
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