Research ExplorerPublicationsFOCAD loss impacts microtubule assembly, G2/M progression an...

FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas

Standard

FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas. / Brand, Frank; Förster, Alisa; Christians, Anne; Bucher, Martin; Thomé, Carina M; Raab, Marc S; Westphal, Manfred; Pietsch, Torsten; von Deimling, Andreas; Reifenberger, Guido; Claus, Peter; Hentschel, Bettina; Weller, Michael; Weber, Ruthild G.

In: ACTA NEUROPATHOL, Vol. 139, No. 1, 01.2020, p. 175-192.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Brand, F, Förster, A, Christians, A, Bucher, M, Thomé, CM, Raab, MS, Westphal, M, Pietsch, T, von Deimling, A, Reifenberger, G, Claus, P, Hentschel, B, Weller, M & Weber, RG 2020, 'FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas', ACTA NEUROPATHOL, vol. 139, no. 1, pp. 175-192. https://doi.org/10.1007/s00401-019-02067-z

APA

Brand, F., Förster, A., Christians, A., Bucher, M., Thomé, C. M., Raab, M. S., Westphal, M., Pietsch, T., von Deimling, A., Reifenberger, G., Claus, P., Hentschel, B., Weller, M., & Weber, R. G. (2020). FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas. ACTA NEUROPATHOL, 139(1), 175-192. https://doi.org/10.1007/s00401-019-02067-z

Vancouver

Brand F, Förster A, Christians A, Bucher M, Thomé CM, Raab MS et al. FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas. ACTA NEUROPATHOL. 2020 Jan;139(1):175-192. https://doi.org/10.1007/s00401-019-02067-z

Bibtex

@article{a75e1738ec8c4046a4854726381ceb48,
title = "FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas",
abstract = "In search of novel genes associated with glioma pathogenesis, we have previously shown frequent deletions of the KIAA1797/FOCAD gene in malignant gliomas, and a tumor suppressor function of the encoded focadhesin impacting proliferation and migration of glioma cells in vitro and in vivo. Here, we examined an association of reduced FOCAD gene copy number with overall survival of patients with astrocytic gliomas, and addressed the molecular mechanisms that govern the suppressive effect of focadhesin on glioma growth. FOCAD loss was associated with inferior outcome in patients with isocitrate dehydrogenase 1 or 2 (IDH)-mutant astrocytic gliomas of WHO grades II-IV. Multivariate analysis considering age at diagnosis as well as IDH mutation, MGMT promoter methylation, and CDKN2A/B homozygous deletion status confirmed reduced FOCAD gene copy number as a prognostic factor for overall survival. Using a yeast two-hybrid screen and pull-down assays, tubulin beta-6 and other tubulin family members were identified as novel focadhesin-interacting partners. Tubulins and focadhesin co-localized to centrosomes where focadhesin was enriched in proximity to centrioles. Focadhesin was recruited to microtubules via its interaction partner SLAIN motif family member 2 and reduced microtubule assembly rates, possibly explaining the focadhesin-dependent decrease in cell migration. During the cell cycle, focadhesin levels peaked in G2/M phase and influenced time-dependent G2/M progression potentially via polo like kinase 1 phosphorylation, providing a possible explanation for focadhesin-dependent cell growth reduction. We conclude that FOCAD loss may promote biological aggressiveness and worsen clinical outcome of diffuse astrocytic gliomas by enhancing microtubule assembly and accelerating G2/M phase progression.",
keywords = "Adult, Aged, Aged, 80 and over, Astrocytoma/genetics, Brain Neoplasms/genetics, Cell Division/genetics, Female, G2 Phase/genetics, Humans, Male, Microtubules/genetics, Middle Aged, Sequence Deletion, Tumor Suppressor Proteins/genetics, Young Adult",
author = "Frank Brand and Alisa F{\"o}rster and Anne Christians and Martin Bucher and Thom{\'e}, {Carina M} and Raab, {Marc S} and Manfred Westphal and Torsten Pietsch and {von Deimling}, Andreas and Guido Reifenberger and Peter Claus and Bettina Hentschel and Michael Weller and Weber, {Ruthild G}",
year = "2020",
month = jan,
doi = "10.1007/s00401-019-02067-z",
language = "English",
volume = "139",
pages = "175--192",
journal = "ACTA NEUROPATHOL",
issn = "0001-6322",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas

AU - Brand, Frank

AU - Förster, Alisa

AU - Christians, Anne

AU - Bucher, Martin

AU - Thomé, Carina M

AU - Raab, Marc S

AU - Westphal, Manfred

AU - Pietsch, Torsten

AU - von Deimling, Andreas

AU - Reifenberger, Guido

AU - Claus, Peter

AU - Hentschel, Bettina

AU - Weller, Michael

AU - Weber, Ruthild G

PY - 2020/1

Y1 - 2020/1

N2 - In search of novel genes associated with glioma pathogenesis, we have previously shown frequent deletions of the KIAA1797/FOCAD gene in malignant gliomas, and a tumor suppressor function of the encoded focadhesin impacting proliferation and migration of glioma cells in vitro and in vivo. Here, we examined an association of reduced FOCAD gene copy number with overall survival of patients with astrocytic gliomas, and addressed the molecular mechanisms that govern the suppressive effect of focadhesin on glioma growth. FOCAD loss was associated with inferior outcome in patients with isocitrate dehydrogenase 1 or 2 (IDH)-mutant astrocytic gliomas of WHO grades II-IV. Multivariate analysis considering age at diagnosis as well as IDH mutation, MGMT promoter methylation, and CDKN2A/B homozygous deletion status confirmed reduced FOCAD gene copy number as a prognostic factor for overall survival. Using a yeast two-hybrid screen and pull-down assays, tubulin beta-6 and other tubulin family members were identified as novel focadhesin-interacting partners. Tubulins and focadhesin co-localized to centrosomes where focadhesin was enriched in proximity to centrioles. Focadhesin was recruited to microtubules via its interaction partner SLAIN motif family member 2 and reduced microtubule assembly rates, possibly explaining the focadhesin-dependent decrease in cell migration. During the cell cycle, focadhesin levels peaked in G2/M phase and influenced time-dependent G2/M progression potentially via polo like kinase 1 phosphorylation, providing a possible explanation for focadhesin-dependent cell growth reduction. We conclude that FOCAD loss may promote biological aggressiveness and worsen clinical outcome of diffuse astrocytic gliomas by enhancing microtubule assembly and accelerating G2/M phase progression.

AB - In search of novel genes associated with glioma pathogenesis, we have previously shown frequent deletions of the KIAA1797/FOCAD gene in malignant gliomas, and a tumor suppressor function of the encoded focadhesin impacting proliferation and migration of glioma cells in vitro and in vivo. Here, we examined an association of reduced FOCAD gene copy number with overall survival of patients with astrocytic gliomas, and addressed the molecular mechanisms that govern the suppressive effect of focadhesin on glioma growth. FOCAD loss was associated with inferior outcome in patients with isocitrate dehydrogenase 1 or 2 (IDH)-mutant astrocytic gliomas of WHO grades II-IV. Multivariate analysis considering age at diagnosis as well as IDH mutation, MGMT promoter methylation, and CDKN2A/B homozygous deletion status confirmed reduced FOCAD gene copy number as a prognostic factor for overall survival. Using a yeast two-hybrid screen and pull-down assays, tubulin beta-6 and other tubulin family members were identified as novel focadhesin-interacting partners. Tubulins and focadhesin co-localized to centrosomes where focadhesin was enriched in proximity to centrioles. Focadhesin was recruited to microtubules via its interaction partner SLAIN motif family member 2 and reduced microtubule assembly rates, possibly explaining the focadhesin-dependent decrease in cell migration. During the cell cycle, focadhesin levels peaked in G2/M phase and influenced time-dependent G2/M progression potentially via polo like kinase 1 phosphorylation, providing a possible explanation for focadhesin-dependent cell growth reduction. We conclude that FOCAD loss may promote biological aggressiveness and worsen clinical outcome of diffuse astrocytic gliomas by enhancing microtubule assembly and accelerating G2/M phase progression.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Astrocytoma/genetics

KW - Brain Neoplasms/genetics

KW - Cell Division/genetics

KW - Female

KW - G2 Phase/genetics

KW - Humans

KW - Male

KW - Microtubules/genetics

KW - Middle Aged

KW - Sequence Deletion

KW - Tumor Suppressor Proteins/genetics

KW - Young Adult

U2 - 10.1007/s00401-019-02067-z

DO - 10.1007/s00401-019-02067-z

M3 - SCORING: Journal article

C2 - 31473790

VL - 139

SP - 175

EP - 192

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 1

ER -