NKCC1 promotes EMT-like process in GBM via RhoA and Rac1 signaling pathways

Journal of Cellular Physiology
Haiwen MaXuejun Yang

Abstract

Glioblastoma is the most common and lethal primary intracranial tumor. As the key regulator of tumor cell volume, sodium-potassium-chloride cotransporter 1 (NKCC1) expression increases along with the malignancy of the glioma, and NKCC1 has been implicated in glioblastoma invasion. However, little is known about the role of NKCC1 in the epithelial-mesenchymal transition-like process in gliomas. We noticed that aberrantly elevated expression of NKCC1 leads to changes in the shape, polarity, and adhesion of cells in glioma. Here, we investigated whether NKCC1 promotes an epithelial-mesenchymal transition (EMT)-like process in gliomas via the RhoA and Rac1 signaling pathways. Pharmacological inhibition and knockdown of NKCC1 both decrease the expressions of mesenchymal markers, such as N-cadherin, vimentin, and snail, whereas these treatments increase the expression of the epithelial marker E-cadherin. These findings indicate that NKCC1 promotes an EMT-like process in gliomas. The underlying mechanism is the facilitation of the binding of Rac1 and RhoA to GTP by NKCC1, which results in a significant enhancement of the EMT-like process. Specific inhibition or knockdown of NKCC1 both attenuate activated Rac1 and RhoA, and the pharmac...Continue Reading

References

Feb 7, 1998·Science·A Hall
Nov 1, 2000·Cell·D Bar-Sagi, A Hall
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Nov 15, 2007·Clinical & Experimental Metastasis·Saskia I J Ellenbroek, John G Collard
May 1, 2008·Experimental Biology and Medicine·Harald Sontheimer
Mar 25, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Kenji HiraokaYoshinori Marunaka
Jun 23, 2010·BMC Cancer·Hong Wei YangMark D Johnson
Jun 24, 2010·Cancer Research·Brian R Haas, Harald Sontheimer
Jul 22, 2010·Molecular Cancer·Svetlana A MikheevaRobert C Rostomily
May 6, 2011·American Journal of Physiology. Cell Physiology·Vishnu Anand Cuddapah, Harald Sontheimer
Jul 26, 2011·Annals of Neurology·Matthias PreusserRoger Stupp
Nov 25, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Stacey Watkins, Harald Sontheimer
Mar 13, 2012·Nature Cell Biology·Wen-Hao YangMuh-Hwa Yang
Jul 5, 2012·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Jehad AlgharabilDandan Sun
Nov 10, 2013·Nature Medicine·Wai Leong Tam, Robert A Weinberg
Jun 20, 2014·World Journal of Gastroenterology : WJG·Atsushi ShiozakiEigo Otsuji
Aug 21, 2014·Cancer Discovery·James P SullivanDaniel A Haber
Jan 27, 2015·Current Medicinal Chemistry·Damin CongDandan Sun
Apr 25, 2015·Expert Review of Anticancer Therapy·Musaddiq AwanSimon S Lo
Sep 17, 2016·Cancer Research·Julia MaierUlrich Rothbauer

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Citations

Aug 17, 2019·Glia·Shanshan SongDandan Sun
Aug 31, 2019·Journal of Oncology·Carlos VelásquezJosé L Fernández-Luna
Dec 9, 2020·International Journal of Molecular Sciences·Tomas Koltai
Mar 13, 2021·Reproductive Sciences·Inha LeeByung Seok Lee
May 25, 2021·The Journal of International Medical Research·Chao-Qun Lin, Lu-Kui Chen

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Methods Mentioned

BETA
xenograft
GTPases
chip
electrophoresis
fluorescence microscopy
transfection
zymography

Software Mentioned

GraphPad Prism
Live Image
GraphPad

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