pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer. / Sauter, Daniel Rafael Peter; Sørensen, Christiane Elisabeth; Rapedius, Markus; Brüggemann, Andrea; Novak, Ivana.

I: B B A - Molecular Basis of Disease, Bind 1862, Nr. 10, 2016, s. 1994-2003.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Sauter, DRP, Sørensen, CE, Rapedius, M, Brüggemann, A & Novak, I 2016, 'pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer', B B A - Molecular Basis of Disease, bind 1862, nr. 10, s. 1994-2003. https://doi.org/10.1016/j.bbadis.2016.07.009

APA

Sauter, D. R. P., Sørensen, C. E., Rapedius, M., Brüggemann, A., & Novak, I. (2016). pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer. B B A - Molecular Basis of Disease, 1862(10), 1994-2003. https://doi.org/10.1016/j.bbadis.2016.07.009

Vancouver

Sauter DRP, Sørensen CE, Rapedius M, Brüggemann A, Novak I. pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer. B B A - Molecular Basis of Disease. 2016;1862(10):1994-2003. https://doi.org/10.1016/j.bbadis.2016.07.009

Author

Sauter, Daniel Rafael Peter ; Sørensen, Christiane Elisabeth ; Rapedius, Markus ; Brüggemann, Andrea ; Novak, Ivana. / pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer. I: B B A - Molecular Basis of Disease. 2016 ; Bind 1862, Nr. 10. s. 1994-2003.

Bibtex

@article{2c7a31da20de46b793f9037897464f43,
title = "pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and new therapeutic targets are urgently needed. One of the hallmarks of cancer is changed pH-homeostasis and potentially pH-sensors may play an important role in cancer cell behavior. Two-pore potassium channels (K2P) are pH-regulated channels that conduct a background K(+) current, which is involved in setting the plasma membrane potential (Vm). Some members of the K2P superfamily were reported as crucial players in driving tumor progression. The aim of this study was to investigate pH-regulated K(+) currents in PDAC cells and determine possible effects on their pathological phenotype. Using a planar high-throughput patch-clamp system (SyncroPatch 384PE) we identified a pH-regulated K(+) current in the PDAC cell line BxPC-3. The current was inhibited by extracellular acidification and intracellular alkalization. Exposure to a set of different K(+) channel inhibitors, and the TREK-1 (K2P2.1)-specific activator BL1249, TREK-1 was identified as the main component of pH-regulated current. A voltage-sensor dye (VF2.1.Cl) was used to monitor effects of pH and BL1249 on Vm in more physiological conditions and TREK-1-mediated current was found as critical player in setting Vm. We assessed a possible role of TREK-1 in PDAC progression using cell proliferation and migration assays and observed similar trends with attenuated proliferation/migration rates in acidic (pH<7.0) and alkaline (pH>7.4) conditions. Notably, BL1249 inhibited both PDAC cell proliferation and migration indicating that hyperpolarization of Vm attenuates cancer cell behavior. TREK-1 may therefore be a promising novel target for PDAC therapy.",
author = "Sauter, {Daniel Rafael Peter} and S{\o}rensen, {Christiane Elisabeth} and Markus Rapedius and Andrea Br{\"u}ggemann and Ivana Novak",
note = "Copyright {\textcopyright} 2016. Published by Elsevier B.V.",
year = "2016",
doi = "10.1016/j.bbadis.2016.07.009",
language = "English",
volume = "1862",
pages = "1994--2003",
journal = "B B A - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier",
number = "10",

}

RIS

TY - JOUR

T1 - pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer

AU - Sauter, Daniel Rafael Peter

AU - Sørensen, Christiane Elisabeth

AU - Rapedius, Markus

AU - Brüggemann, Andrea

AU - Novak, Ivana

N1 - Copyright © 2016. Published by Elsevier B.V.

PY - 2016

Y1 - 2016

N2 - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and new therapeutic targets are urgently needed. One of the hallmarks of cancer is changed pH-homeostasis and potentially pH-sensors may play an important role in cancer cell behavior. Two-pore potassium channels (K2P) are pH-regulated channels that conduct a background K(+) current, which is involved in setting the plasma membrane potential (Vm). Some members of the K2P superfamily were reported as crucial players in driving tumor progression. The aim of this study was to investigate pH-regulated K(+) currents in PDAC cells and determine possible effects on their pathological phenotype. Using a planar high-throughput patch-clamp system (SyncroPatch 384PE) we identified a pH-regulated K(+) current in the PDAC cell line BxPC-3. The current was inhibited by extracellular acidification and intracellular alkalization. Exposure to a set of different K(+) channel inhibitors, and the TREK-1 (K2P2.1)-specific activator BL1249, TREK-1 was identified as the main component of pH-regulated current. A voltage-sensor dye (VF2.1.Cl) was used to monitor effects of pH and BL1249 on Vm in more physiological conditions and TREK-1-mediated current was found as critical player in setting Vm. We assessed a possible role of TREK-1 in PDAC progression using cell proliferation and migration assays and observed similar trends with attenuated proliferation/migration rates in acidic (pH<7.0) and alkaline (pH>7.4) conditions. Notably, BL1249 inhibited both PDAC cell proliferation and migration indicating that hyperpolarization of Vm attenuates cancer cell behavior. TREK-1 may therefore be a promising novel target for PDAC therapy.

AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and new therapeutic targets are urgently needed. One of the hallmarks of cancer is changed pH-homeostasis and potentially pH-sensors may play an important role in cancer cell behavior. Two-pore potassium channels (K2P) are pH-regulated channels that conduct a background K(+) current, which is involved in setting the plasma membrane potential (Vm). Some members of the K2P superfamily were reported as crucial players in driving tumor progression. The aim of this study was to investigate pH-regulated K(+) currents in PDAC cells and determine possible effects on their pathological phenotype. Using a planar high-throughput patch-clamp system (SyncroPatch 384PE) we identified a pH-regulated K(+) current in the PDAC cell line BxPC-3. The current was inhibited by extracellular acidification and intracellular alkalization. Exposure to a set of different K(+) channel inhibitors, and the TREK-1 (K2P2.1)-specific activator BL1249, TREK-1 was identified as the main component of pH-regulated current. A voltage-sensor dye (VF2.1.Cl) was used to monitor effects of pH and BL1249 on Vm in more physiological conditions and TREK-1-mediated current was found as critical player in setting Vm. We assessed a possible role of TREK-1 in PDAC progression using cell proliferation and migration assays and observed similar trends with attenuated proliferation/migration rates in acidic (pH<7.0) and alkaline (pH>7.4) conditions. Notably, BL1249 inhibited both PDAC cell proliferation and migration indicating that hyperpolarization of Vm attenuates cancer cell behavior. TREK-1 may therefore be a promising novel target for PDAC therapy.

U2 - 10.1016/j.bbadis.2016.07.009

DO - 10.1016/j.bbadis.2016.07.009

M3 - Journal article

C2 - 27443495

VL - 1862

SP - 1994

EP - 2003

JO - B B A - Molecular Basis of Disease

JF - B B A - Molecular Basis of Disease

SN - 0925-4439

IS - 10

ER -

ID: 164453485