How Dysregulated Ion Channels and Transporters Take a Hand in Esophageal, Liver, and Colorectal Cancer

Abstract

Over the last two decades, the understanding of how dysregulated ion channels and transporters are involved in carcinogenesis and tumor growth and progression, including invasiveness and metastasis, has been increasing exponentially. The present review specifies virtually all ion channels and transporters whose faulty expression or regulation contributes to esophageal, hepatocellular, and colorectal cancer. The variety reaches from Ca²⁺, K⁺, Na⁺, and Cl⁻ channels over divalent metal transporters, Na⁺ or Cl⁻ coupled Ca²⁺, HCO₃⁻ and H⁺ exchangers to monocarboxylate carriers and organic anion and cation transporters. In several cases, the underlying mechanisms by which these ion channels/transporters are interwoven with malignancies have been fully or at least partially unveiled. Ca²⁺, Akt/NF-κB, and Ca²⁺- or pH-dependent Wnt/β-catenin signaling emerge as cross points through which ion channels/transporters interfere with gene expression, modulate cell proliferation, trigger epithelial-to-mesenchymal transition, and promote cell motility and metastasis. Also miRs, lncRNAs, and DNA methylation represent potential links between the misexpression of genes encoding for ion channels/transporters, their malfunctioning, and cancer. The knowledge of all these molecular interactions has provided the basis for therapeutic strategies and approaches, some of which will be broached in this review.