Overexpression of Large‐Conductance Calcium‐Activated Potassium Channels in Human Glioblastoma Stem‐Like Cells and Their Role in Cell Migration

Abstract

Glioblastomas (GBMs) are brain tumors characterized by diffuse invasion of cancer cells into the healthy brain parenchyma, and establishment of secondary foci. GBM cells abundantly express large-conductance, calcium-activated potassium (BK) channels that are thought to promote cell invasion. Recent evidence suggests that the GBM high invasive potential mainly originates from a pool of stem-like cells, but the expression and function of BK channels in this cell subpopulation have not been studied. We investigated the expression of BK channels in GBM stem-like cells using electrophysiological and immunochemical techniques, and assessed their involvement in the migratory process of this important cell subpopulation. In U87-MG cells, BK channel expression and function were markedly upregulated by growth conditions that enriched the culture in GBM stem-like cells (U87-NS). Cytofluorimetric analysis further confirmed the appearance of a cell subpopulation that co-expressed high levels of BK channels and CD133, as well as other stem cell markers. A similar association was also found in cells derived from freshly resected GBM biopsies. Finally, transwell migration tests showed that U87-NS cells migration was much more sensitive to BK channel block than U87-MG cells. Our data show that BK channels are highly expressed in GBM stem-like cells, and participate to their high migratory activity. J. Cell. Physiol. 232: 2478-2488, 2017. © 2016 Wiley Periodicals, Inc.

The extracellular loop of the auxiliary β1-subunit is involved in the regulation of BKCa channel mechanosensitivity

“…The large-conductance Ca 2ϩ -activated potassium (BK Ca ) channels play a crucial role in many physiological processes such as regulation of smooth muscle tone (25), neuronal firing (16), cell differentiation (30,33), and cell migration (26) and are known to be mechanosensitive ion channels (29). However, the detailed molecular mechanism that allows BK Ca channels to be activated by membrane stretch remains unclear.…”

Synergistic effect of TRAIL and irradiation in elimination of glioblastoma stem-like cells

“…GSLC was the most vicious cell type in GBM cells, involving in treatment resistance and recurrence of GBMs [2,5]. In order to study the properties of GSLCs, we firstly enriched them from two GBM cell lines using serum-free medium supplemented with growth factors as the literature reported [29][30][31]. CD133 is still the most commonly used cell markers of glioma stem cells [6,32] despite some disputes [33].…”

Emerging roles for multifunctional ion channel auxiliary subunits in cancer

“…K + channels represent an extensive superfamily of channels, many of which have been implicated in regulating key elements of tumour progression [ [116] , [117] , [118] ]. Here, we focus on the function and involvement in cancer of the auxiliary subunits of the voltage-gated K + channel (VGKC), BK channel and K ir channel complexes ( Fig.…”

“…BK channels are expressed in most tissues and are involved in a range of functions, such as learning and memory [ 183 ], pain modulation [ 184 ] and blood pressure regulation [ 185 ]. BK channels are upregulated in glioblastoma primary cells and promote proliferation and invasion [ 117 , 186 ]. BK channel function is modulated by two groups of auxiliary subunits- BKβ 1-4 and BKγ 1-4 , both double-pass membrane proteins.…”