Withaferin A suppresses breast cancer cell proliferation by inhibition of the two-pore domain potassium (K2P9) channel TASK-3.

Withaferin A (WFA), a C,C-epoxy steroidal lactone isolated from the medicinal plant Withania somnifera (L.) Dunal, inhibits growth of tumor cells in different cancer types. However, the mechanisms underlying the effect of WFA on tumor cells are not fully understood.

Elucidating the Structural Basis of the Intracellular pH Sensing Mechanism of TASK-2 KP Channels.

Two-pore domain potassium (KP) channels maintain the cell's background conductance by stabilizing the resting membrane potential. They assemble as dimers possessing four transmembrane helices in each subunit. KP channels were crystallized in "up" and "down" states.

Correction: Concha, G., et al. The Insensitivity of TASK-3 KP Channels to External Tetraethylammonium (TEA) Partially Depends on the Cap Structure. 2018, , 2437.

We would like to submit the following correction to our published paper [...

Discovery of Novel TASK-3 Channel Blockers Using a Pharmacophore-Based Virtual Screening.

TASK-3 is a two-pore domain potassium (K) channel highly expressed in the hippocampus, cerebellum, and cortex. TASK-3 has been identified as an oncogenic potassium channel and it is overexpressed in different cancer types. For this reason, the development of new TASK-3 blockers could influence the pharmacological treatment of cancer and several neurological conditions.

HCN Channels: New Therapeutic Targets for Pain Treatment.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are highly regulated proteins which respond to different cellular stimuli. The HCN currents (I) mediated by HCN1 and HCN2 drive the repetitive firing in nociceptive neurons. The role of HCN channels in pain has been widely investigated as targets for the development of new therapeutic drugs, but the comprehensive design of HCN channel modulators has been restricted due to the lack of crystallographic data.

The Insensitivity of TASK-3 K₂P Channels to External Tetraethylammonium (TEA) Partially Depends on the Cap Structure.

Two-pore domain K⁺ channels (K₂P) display a characteristic extracellular cap structure formed by two M1-P1 linkers, the functional role of which is poorly understood. It has been proposed that the presence of the cap explains the insensitivity of K₂P channels to several K⁺ channel blockers including tetraethylammonium (TEA). We have explored this hypothesis using mutagenesis and functional analysis, followed by molecular simulations.

TASK-3 Downregulation Triggers Cellular Senescence and Growth Inhibition in Breast Cancer Cell Lines.

TASK-3 potassium channels are believed to promote proliferation and survival of cancer cells, in part, by augmenting their resistance to both hypoxia and serum deprivation. While overexpression of TASK-3 is frequently observed in cancers, the understanding of its role and regulation during tumorigenesis remains incomplete. Here, we evaluated the effect of reducing the expression of TASK-3 in MDA-MB-231 and MCF-10F human mammary epithelial cell lines through small hairpin RNA (shRNA)-mediated knockdown.