DECREASED EXPRESSION OF NHE3 IN COLON CANCER EPITHELIUM IS ASSOCIATED WITH DNA DAMAGE, INCREASED LOCAL INFLAMMATION AND TUMOR GROWTH

Dysregulation of intracellular and extracellular pH in cancer is thought to contribute to extracellular matrix remodeling, cancer metastasis, and favors cell migration and proliferation. Although the primary attention has been focused on the role of the ubiquitous Na+/H+ exchanger 1 isoform (SLC9A1), the role of NHE3 (SLC9A3), the predominant apical isoform in colonic surface epithelium in the pathogenesis of colon cancer has not been investigated. Our findings suggest that loss of NHE3 in the surface epithelium of colonic tumors has profound consequences for cancer progression and behavior.