HIF1A and neoplasm: Notably, acidic stress may upregulate dysadherin via the activation of pH-responsive transcription factors such as HIF-1α and NF-κB, for which putative binding sites were identified in the FXYD5 promoter region (Supplementary Fig. 11).45,46 Furthermore, the strong positive correlation between FXYD5 and multiple acidosis-associated genes supports its broader role in facilitating tumor adaptation to acidic microenvironments.