Deeper and Deeper on the Role of BK and Kir4.1 Channels in Glioblastoma Invasiveness: A Novel Summative Mechanism?

Abstract

In the last decades, increasing evidence has revealed that a large number of channel protein and ion pumps exhibit impaired expression in cancers. This dysregulation is responsible for high proliferative rates as well as migration and invasiveness, reflected in the recently coined term oncochannelopathies. In glioblastoma (GBM), the most invasive and aggressive primary brain tumor, GBM cells modify their ionic equilibrium in order to change their volume as a necessary step prior to migration. This mechanism involves increased expression of BK channels and downregulation of the normally widespread Kir4.1 channels, as noted in GBM biopsies from patients. Despite a large body of work implicating BK channels in migration in response to an artificial intracellular calcium rise, little is known about how this channel acts in GBM cells at resting membrane potential (RMP), as compared to other channels that are constitutively open, such as Kir4.1. In this review we propose that a residual fraction of functionally active Kir4.1 channels mediates a small, but continuous, efflux of potassium at the more depolarized RMP of GBM cells. In addition, coinciding with transient membrane deformation and the intracellular rise in calcium concentration, brief activity of BK channels can induce massive and rapid cytosolic water loss that reduces cell volume (cell shrinkage), a necessary step for migration within the brain parenchyma.

The Mössbauer effect using 57Fe-ferrabisdicarbollide ([o-57FESAN]−): a glance into the potential of a low-dose approach for glioblastoma radiotherapy

“…These changes may have consequences for the level of growth control, cell volume and activity regulation in cancer cells. [52][53][54] Nevertheless, the interpretation of these results requires further experiments.…”

NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines

“…In fact, alterations in Em (depolarization or hyperpolarization) have been proposed to play a crucial role in controlling the cell cycle, thus suggesting a relevance of BK channel in cancer proliferation, invasion, and metastasis [ 12 ]. In this regard, in some studies, activation of BK channels has been reported to slow proliferation and invasion of breast cancer cells, or in glioblastoma cells [ 11 , 13 , 14 , 15 , 16 ]. In contrast, in other studies, anti-cancer action has been described for inhibition of BK channels, namely, in metastatic breast cancer cells, as well as in endometrial cancer cells [ 17 , 18 , 19 ].…”

Calcium Signalling in Medulloblastoma: An In Silico Analysis of the Expression of Calcium Regulating Genes in Patient Samples

“…For instance, potassium-stimulated depolarization facilitates Ca 2+ entry through T-type (low depolarization potential) or L-type (higher depolarization potential) channels [ 33 ]. On the other hand, calcium-activated potassium channels (BK channels), stimulated by Ca 2+ or Mg 2+ , are responsible for the majority of K + conductance throughout the cell membrane [ 34 , 35 ]. In MB, voltage-gated potassium channel EAG2 is upregulated in human-derived MB cells, where it promotes tumour growth in vitro [ 36 , 37 ].…”