Membrane-Depolarizing Channel Blockers Induce Selective Glioma
Cell Death by Impairing Nutrient Transport and Unfolded
Protein/Amino Acid Responses

J 2017

Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses

NIKLASSON, M., G. MADDALO, Zuzana ŠRÁMKOVÁ, E. MUTLU, S. WEE et. al.

Základní údaje

Originální název

Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses

Autoři

NIKLASSON, M. (752 Švédsko), G. MADDALO (528 Nizozemské království), Zuzana ŠRÁMKOVÁ (703 Slovensko, domácí), E. MUTLU (578 Norsko), S. WEE (752 Švédsko), Petra SEKYROVÁ (203 Česká republika, domácí), L. SCHMIDT (752 Švédsko), N. FRITZ (752 Švédsko), I. DEHNISCH (752 Švédsko), G. KYRIATZIS (752 Švédsko), Michaela KRAFČÍKOVÁ (703 Slovensko, domácí), B.B. CARSON (840 Spojené státy), J.M. FEENSTRA (752 Švédsko), V.D. MARINESCU (752 Švédsko), A. SEGERMAN (752 Švédsko), M. HARALDSSON (752 Švédsko), A.L. GUSTAVSSON (752 Švédsko), L.G.J. HAMMARSTROM (752 Švédsko), A.J. JENSEN (752 Švédsko), L. UHRBOM (752 Švédsko), A.F.M. ALTELAAR (528 Nizozemské království), S. LINNARSSON (752 Švédsko), P. UHLEN (752 Švédsko), Lukáš TRANTÍREK (203 Česká republika, garant, domácí), C.T. VINCENT (752 Švédsko), S. NELANDER (752 Švédsko), P.O. ENGER (752 Švédsko) a Michael ANDÄNG (752 Švédsko, domácí)

Vydání

Cancer Research, PHILADELPHIA, AMER ASSOC CANCER RESEARCH, 2017, 0008-5472

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.130

Kód RIV

RIV/00216224:14740/17:00095470

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1158/0008-5472.CAN-16-2274

UT WoS

000398262400020

Klíčová slova anglicky

TUMOR-INITIATING CELLS; CANCER STEM-CELLS; T-TYPE; HUMAN GLIOBLASTOMA; MULTIDRUG-RESISTANCE; GENE-EXPRESSION; HIGH-THROUGHPUT; INHIBITION; CULTURE; IDENTIFICATION

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 26. 4. 2018 12:46, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstreamsignaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. Our results suggest new therapeutic targets to attack aggressive gliomas.

Návaznosti

GA15-20818S, projekt VaV

Název: Cílená terapie proti rezistentím kmenovým buňkám gliomového nádoru - kontrola přísunu živin pomocí iontových kanálů

Investor: Grantová agentura ČR, Cílená terapie proti rezistentím kmenovým buňkám gliomového nádoru - kontrola přísunu živin pomocí iontových kanálů

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

NIKLASSON, M., G. MADDALO, Zuzana ŠRÁMKOVÁ, E. MUTLU, S. WEE, Petra SEKYROVÁ, L. SCHMIDT, N. FRITZ, I. DEHNISCH, G. KYRIATZIS, Michaela KRAFČÍKOVÁ, B.B. CARSON, J.M. FEENSTRA, V.D. MARINESCU, A. SEGERMAN, M. HARALDSSON, A.L. GUSTAVSSON, L.G.J. HAMMARSTROM, A.J. JENSEN, L. UHRBOM, A.F.M. ALTELAAR, S. LINNARSSON, P. UHLEN, Lukáš TRANTÍREK, C.T. VINCENT, S. NELANDER, P.O. ENGER a Michael ANDÄNG. Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses. Cancer Research. PHILADELPHIA: AMER ASSOC CANCER RESEARCH, 2017, roč. 77, č. 7, s. 1741-1752. ISSN 0008-5472. Dostupné z: https://dx.doi.org/10.1158/0008-5472.CAN-16-2274.

@article{1406729,
   author = {Niklasson, M. and Maddalo, G. and Šrámková, Zuzana and Mutlu, E. and Wee, S. and Sekyrová, Petra and Schmidt, L. and Fritz, N. and Dehnisch, I. and Kyriatzis, G. and Krafčíková, Michaela and Carson, B.B. and Feenstra, J.M. and Marinescu, V.D. and Segerman, A. and Haraldsson, M. and Gustavsson, A.L. and Hammarstrom, L.G.J. and Jensen, A.J. and Uhrbom, L. and Altelaar, A.F.M. and Linnarsson, S. and Uhlen, P. and Trantírek, Lukáš and Vincent, C.T. and Nelander, S. and Enger, P.O. and Andäng, Michael},
   article_location = {PHILADELPHIA},
   article_number = {7},
   doi = {http://dx.doi.org/10.1158/0008-5472.CAN-16-2274},
   keywords = {TUMOR-INITIATING CELLS; CANCER STEM-CELLS; T-TYPE; HUMAN GLIOBLASTOMA; MULTIDRUG-RESISTANCE; GENE-EXPRESSION; HIGH-THROUGHPUT; INHIBITION; CULTURE; IDENTIFICATION},
   language = {eng},
   issn = {0008-5472},
   journal = {Cancer Research},
   title = {Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses},
   url = {http://cancerres.aacrjournals.org/content/77/7/1741.short},
   volume = {77},
   year = {2017}
}

TY  - JOUR
ID  - 1406729
AU  - Niklasson, M. - Maddalo, G. - Šrámková, Zuzana - Mutlu, E. - Wee, S. - Sekyrová, Petra - Schmidt, L. - Fritz, N. - Dehnisch, I. - Kyriatzis, G. - Krafčíková, Michaela - Carson, B.B. - Feenstra, J.M. - Marinescu, V.D. - Segerman, A. - Haraldsson, M. - Gustavsson, A.L. - Hammarstrom, L.G.J. - Jensen, A.J. - Uhrbom, L. - Altelaar, A.F.M. - Linnarsson, S. - Uhlen, P. - Trantírek, Lukáš - Vincent, C.T. - Nelander, S. - Enger, P.O. - Andäng, Michael
PY  - 2017
TI  - Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses
JF  - Cancer Research
VL  - 77
IS  - 7
SP  - 1741-1752
EP  - 1741-1752
PB  - AMER ASSOC CANCER RESEARCH
SN  - 00085472
KW  - TUMOR-INITIATING CELLS
KW  - CANCER STEM-CELLS
KW  - T-TYPE
KW  - HUMAN GLIOBLASTOMA
KW  - MULTIDRUG-RESISTANCE
KW  - GENE-EXPRESSION
KW  - HIGH-THROUGHPUT
KW  - INHIBITION
KW  - CULTURE
KW  - IDENTIFICATION
UR  - http://cancerres.aacrjournals.org/content/77/7/1741.short
L2  - http://cancerres.aacrjournals.org/content/77/7/1741.short
N2  - Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstreamsignaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. Our results suggest new therapeutic targets to attack aggressive gliomas.
ER  -

NIKLASSON, M., G. MADDALO, Zuzana ŠRÁMKOVÁ, E. MUTLU, S. WEE, Petra SEKYROVÁ, L. SCHMIDT, N. FRITZ, I. DEHNISCH, G. KYRIATZIS, Michaela KRAFČÍKOVÁ, B.B. CARSON, J.M. FEENSTRA, V.D. MARINESCU, A. SEGERMAN, M. HARALDSSON, A.L. GUSTAVSSON, L.G.J. HAMMARSTROM, A.J. JENSEN, L. UHRBOM, A.F.M. ALTELAAR, S. LINNARSSON, P. UHLEN, Lukáš TRANTÍREK, C.T. VINCENT, S. NELANDER, P.O. ENGER a Michael ANDÄNG. Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses. \textit{Cancer Research}. PHILADELPHIA: AMER ASSOC CANCER RESEARCH, 2017, roč.~77, č.~7, s.~1741-1752. ISSN~0008-5472. Dostupné z: https://dx.doi.org/10.1158/0008-5472.CAN-16-2274.

Podrobný výpis o publikaci