Interplay Between Ion Channels and the Wnt/β-Catenin Signaling Pathway in Cancers

Abstract

Increasing evidence point out the important roles of ion channels in the physiopathology of cancers, so that these proteins are now considered as potential new therapeutic targets and biomarkers in this disease. Indeed, ion channels have been largely described to participate in many hallmarks of cancers such as migration, invasion, proliferation, angiogenesis, and resistance to apoptosis. At the molecular level, the development of cancers is characterised by alterations in transduction pathways that control cell behaviors. However, the interactions between ion channels and cancer-related signaling pathways are poorly understood so far. Nevertheless, a limited number of reports have recently addressed this important issue, especially regarding the interaction between ion channels and one of the main driving forces for cancer development: the Wnt/b-catenin signaling pathway. In this review, we propose to explore and discuss the current knowledge regarding the interplay between ion channels and the Wnt/b-catenin signaling pathway in cancers.

TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review)

“…The Wnt/β-catenin pathway is the canonical Wnt signaling pathway, also known as the 'β-catenin-dependent' Wnt pathway. Wnt/β-catenin has been proven to play an important role in body development and growth, tumor, cardiovascular disease, musculoskeletal diseases, and also respiratory disease (76)(77)(78). In normal conditions, the glycogen synthase kinase-3β (GSK-3β) combines with the β-catenin, axis inhibition protein (Axin) and adenomatous polyposis coli (APC) to form a complex.…”

“…In normal conditions, the glycogen synthase kinase-3β (GSK-3β) combines with the β-catenin, axis inhibition protein (Axin) and adenomatous polyposis coli (APC) to form a complex. When the Wnt/β-catenin was activated, the complex degraded, while β-catenin was not degraded and translocated into the nucleus ( 77 ).…”

From Channels to Canonical Wnt Signaling: A Pathological Perspective

“…Some of them have been summed up and functionally divided into onco-suppressors and onco-channels in Tables 2 and 3, specifically focusing on channels involved in regulating Wnt signaling in cancer disease formation and progression. Moreover, ion channels and Wnt signaling interplay in tumors have been thoroughly and nicely reviewed by Mauss et al [50].…”

“…Particularly, we will focus on the newest findings on ion channels modulation of Wnt signaling, unraveling novel insights in cancer and neurological diseases. The following sections will update the state of the art of the widely reported role of channels in canonical Wnt signaling (see several examples in Table 1 , further details can be found in [ 50 ]) and will provide a comprehensive and focused point of view on those events.…”

“…Increasing evidence point out the involvement of ion channels belonging to all the five main ion channels family (potassium, chloride, sodium, calcium and non-selective ion channels) in cancer physiopathology [ 50 ]. Some of them have been summed up and functionally divided into onco-suppressors and onco-channels in Table 2 and Table 3 , specifically focusing on channels involved in regulating Wnt signaling in cancer disease formation and progression.…”