Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation.

PLoS Biology
Tomas Garzon-MuvdiAlfredo Quiñones-Hinojosa

Abstract

Glioblastoma (GB) is a highly invasive and lethal brain tumor due to its universal recurrence. Although it has been suggested that the electroneutral Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) can play a role in glioma cell migration, the precise mechanism by which this ion transporter contributes to GB aggressiveness remains poorly understood. Here, we focused on the role of NKCC1 in the invasion of human primary glioma cells in vitro and in vivo. NKCC1 expression levels were significantly higher in GB and anaplastic astrocytoma tissues than in grade II glioma and normal cortex. Pharmacological inhibition and shRNA-mediated knockdown of NKCC1 expression led to decreased cell migration and invasion in vitro and in vivo. Surprisingly, knockdown of NKCC1 in glioma cells resulted in the formation of significantly larger focal adhesions and cell traction forces that were approximately 40% lower than control cells. Epidermal growth factor (EGF), which promotes migration of glioma cells, increased the phosphorylation of NKCC1 through a PI3K-dependant mechanism. This finding is potentially related to WNK kinases. Taken together, our findings suggest that NKCC1 modulates migration of glioma cells by two distinct mechanisms: (1) through t...Continue Reading

References

Jun 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D E BirkR L Trelstad
Jan 1, 1988·Cell Motility and the Cytoskeleton·C S Izzard
Sep 1, 1983·The American Journal of Physiology·M Haas, T J McManus
Sep 1, 1995·Pflügers Archiv : European journal of physiology·A SchwabH Oberleithner
Nov 1, 1995·The Journal of Clinical Investigation·J LimD M Kaji
Mar 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·D E BirkE I Zycband
Dec 1, 1994·The American Journal of Physiology·S RosengrenG S Worthen
Jul 1, 1994·Annals of Biomedical Engineering·R B DickinsonR T Tranquillo
Jan 1, 1994·American Journal of Respiratory Cell and Molecular Biology·G S WorthenD M Hyde
Feb 9, 1996·Cell·D A Lauffenburger, A F Horwitz
Feb 11, 1996·The American Journal of Physiology·C Lytle, B Forbush
Feb 11, 1998·Physiological Reviews·F LangD Häussinger
Jun 6, 1998·The Journal of Biological Chemistry·P IsenringB Forbush
Jul 14, 1998·Nature Medicine·J KononenO P Kallioniemi
Jul 22, 1998·Journal of Bioenergetics and Biomembranes·M Haas, B Forbush
Oct 3, 1998·Trends in Biochemical Sciences·A H ChishtiK B Hoover
Dec 2, 1999·Experimental Cell Research·B Vanhaesebroeck, M D Waterfield
Jan 29, 2000·Pflügers Archiv : European journal of physiology·S W SchneiderA Schwab
Apr 25, 2000·The Journal of General Physiology·M KleinA Schwab
Jul 27, 2000·The Journal of Biological Chemistry·A MercadoG Gamba
Feb 8, 2002·American Journal of Physiology. Cell Physiology·James P ButlerJeffrey J Fredberg
Feb 8, 2002·American Journal of Physiology. Cell Physiology·Ning WangDimitrije Stamenović
Mar 14, 2002·Current Opinion in Cell Biology·Len StephensPhillip Hawkins
Mar 14, 2002·Current Opinion in Cell Biology·Sheryl P Denker, Diane L Barber
May 23, 2002·Human Molecular Genetics·Rachel MyerowitzRichard L Proia
Jul 11, 2002·Brain Research. Molecular Brain Research·Luyan SongDavid B Mount
Jul 30, 2002·The Journal of Biological Chemistry·Andreas W FlemmerBiff Forbush
Sep 13, 2002·American Journal of Physiology. Cell Physiology·Iva Marija Tolić-NørrelykkeNing Wang
Oct 10, 2002·American Journal of Physiology. Cell Physiology·Christian Lytle, Thomas McManus
Dec 18, 2002·The Journal of Cell Biology·Sheryl P Denker, Diane L Barber
Jan 8, 2003·The Journal of Cell Biology·Metello InnocentiGiorgio Scita
Oct 31, 2003·Cancer Cell·Ji LuoLewis C Cantley
Dec 31, 2003·Molecular and Cellular Neurosciences·John A BoockvarDonald M O'Rourke

❮ Previous
Next ❯

Citations

Feb 1, 2014·Neuro-oncology·Kaisorn L Chaichana, Alfredo Quinones-Hinojosa
Jun 21, 2014·Nature Reviews. Neuroscience·Vishnu Anand CuddapahHarald Sontheimer
Nov 26, 2013·Molecular Neurobiology·Eli T SayeghAndrew T Parsa
Sep 24, 2014·Journal of Proteome Research·Annalisa NicastriGiovanni Cuda
Dec 5, 2012·BMC Medical Genomics·Ahmed SadequeSandra L Rodriguez-Zas
Mar 14, 2013·The Journal of Biological Chemistry·Zhaohuan ZhangCheng He
Mar 12, 2016·Nature Reviews. Neurology·Gilles Huberfeld, Charles J Vecht
Mar 20, 2016·Neoplasia : an International Journal for Oncology Research·Jessica TilghmanJohn Laterra
Feb 24, 2015·Cancer Biology & Therapy·A-Rum YoonSteven S An
Nov 13, 2014·CPT: Pharmacometrics & Systems Pharmacology·L WangS Li
Apr 15, 2015·Nature Reviews. Nephrology·Tamina Seeger-NukpezahErica A Golemis
Aug 29, 2013·The Biochemical Journal·Takayasu MoriShinichi Uchida
Jan 17, 2015·Cell Death and Differentiation·Y W MoonG Giaccone
May 20, 2015·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Wiebke C BasseMarkus Bleich
Jan 11, 2013·Journal of Hypertension·María Chávez-CanalesGerardo Gamba
Apr 9, 2015·Frontiers in Cellular Neuroscience·Alisa Litan, Sigrid A Langhans
Oct 1, 2014·Stem Cells and Development·Mingxin ZhuAlfredo Quiñones-Hinojosa
Jul 18, 2016·European Biophysics Journal : EBJ·Emily G Thompson, Harald Sontheimer
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yawen MaYunhui Liu
Feb 2, 2017·Scientific Reports·Hao-Yuan WangShi-Zhong Zhang
Feb 9, 2017·Cell Metabolism·Masoud ShekarabiKristopher T Kahle
Feb 11, 2015·Nature Communications·Kalyan C KondapalliRajini Rao
Jun 22, 2018·Journal of Neuroinflammation·Wen-di LuoBi-Wen Peng
Nov 6, 2018·Cell Communication and Signaling : CCS·Sachith Gallolu KankanamalageMelanie H Cobb
Nov 14, 2019·Nature Neuroscience·Erik JungFrank Winkler
Jun 18, 2020·Journal of Clinical Pathology·Makoto MuraseMasahiro Toda
Nov 1, 2014·CPT: Pharmacometrics & Systems Pharmacology·L WangS Li
Oct 21, 2015·Journal of Experimental & Clinical Cancer Research : CR·Barbara GuerraOlaf-Georg Issinger
Sep 12, 2018·Cancers·Gabriel Valentín-GuillamaLilia Y Kucheryavykh
May 19, 2019·Cellular and Molecular Life Sciences : CMLS·Natanael ZarcoHugo Guerrero-Cázares
Sep 4, 2015·Journal of Neuro-oncology·Ole J SimonSven G Meuth
Jan 20, 2017·Frontiers in Cell and Developmental Biology·Richa SinghMauricio Di Fulvio

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
immunoprecipitation
pulls down
surgical resection
co-immunoprecipitation assay
nucleotide exchange
Flow
Assay
scanning electron microscopy

Software Mentioned

SAS
Image J
FRIDA
Sigma Plot
MATLAB

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Actin, Myosin & Cell Movement

Contractile forces generated by the actin-myosin cytoskeleton are critical for morphogenesis, but the cellular and molecular mechanisms of contraction have been elusive for many cell shape changes and movements. Here is the latest research on the roles of actin and myosin in cell movement.

Biophysics of Adhesion

Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. It is also essential for infectious organisms, such as bacteria or viruses, to cause diseases. Understanding the biophysics of cell adhesion can help understand these diseases. Discover the latest research on the biophysics of adhesion here.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Advanced Imaging of Cellular Signaling

Cell signaling is a vital mechanism for communication within cells and outside with the environment. Several different signaling pathways have been found and advanced imaging techniques are being developed to visualize the molecules involved in these signaling pathways. Find the latest research in advanced imaging of cellular signaling here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
José Ponce-CoriaGerardo Gamba
Journal of the American Society of Nephrology : JASN
Mark GloverKevin M O'Shaughnessy
© 2021 Meta ULC. All rights reserved