DIAPH1 regulates chromosomal instability of cancer cells by controlling microtubule dynamics
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DIAPH1 regulates chromosomal instability of cancer cells by controlling microtubule dynamics. / Miao, Shumin; Schäfer, Paula; Nojszewski, Jessica; Meyer, Felix; Windhorst, Sabine.
in: EUR J CELL BIOL, Jahrgang 100, Nr. 3, 151156, 04.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - DIAPH1 regulates chromosomal instability of cancer cells by controlling microtubule dynamics
AU - Miao, Shumin
AU - Schäfer, Paula
AU - Nojszewski, Jessica
AU - Meyer, Felix
AU - Windhorst, Sabine
N1 - Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - Chromosomal instability (CIN) is a hallmark of cancer, resulting from misalignment and missegregation of chromosomes during meta- and anaphase, due to non-precise regulation of spindle-MT dynamics. Diaphanous Related Formin 1 (DIAPH1) is an actin nucleator and also binds microtubule (MT) with high affinity. In this study, we analyzed the role of DIAPH1 in regulation of spindle MT-dynamics and CIN in HT29 and HCT-116 colorectal cancer (CRC) cells. Our data show that down-regulation of DIAPH1 in these cell lines decreased spindle-MT speed by 50 % and the fraction of cells with misaligned and missegregated chromosomes was significantly increased. Furthermore, in HCT-116 DIAPH1 depleted cells deviation of chromosome number was elevated and the number of cells with micronuclei and cytosolic DNA was increased in both DIAPH1-knock down cell lines. In line with these results, database analysis revealed a significant correlation with low DIAPH1 mRNA expression and aneuploidy. Thus, DIAPH1 is substantially involved in the control of CIN in CRC cells. Since in vitro, DIAPH1 directly increased MT-polymerization, we assume that DIAPH1 controls CIN by regulating spindle-MT dynamics.
AB - Chromosomal instability (CIN) is a hallmark of cancer, resulting from misalignment and missegregation of chromosomes during meta- and anaphase, due to non-precise regulation of spindle-MT dynamics. Diaphanous Related Formin 1 (DIAPH1) is an actin nucleator and also binds microtubule (MT) with high affinity. In this study, we analyzed the role of DIAPH1 in regulation of spindle MT-dynamics and CIN in HT29 and HCT-116 colorectal cancer (CRC) cells. Our data show that down-regulation of DIAPH1 in these cell lines decreased spindle-MT speed by 50 % and the fraction of cells with misaligned and missegregated chromosomes was significantly increased. Furthermore, in HCT-116 DIAPH1 depleted cells deviation of chromosome number was elevated and the number of cells with micronuclei and cytosolic DNA was increased in both DIAPH1-knock down cell lines. In line with these results, database analysis revealed a significant correlation with low DIAPH1 mRNA expression and aneuploidy. Thus, DIAPH1 is substantially involved in the control of CIN in CRC cells. Since in vitro, DIAPH1 directly increased MT-polymerization, we assume that DIAPH1 controls CIN by regulating spindle-MT dynamics.
KW - Cell Line, Tumor
KW - Chromosomal Instability/genetics
KW - Colonic Neoplasms/genetics
KW - Formins/metabolism
KW - Humans
KW - Microtubules/metabolism
U2 - 10.1016/j.ejcb.2021.151156
DO - 10.1016/j.ejcb.2021.151156
M3 - SCORING: Journal article
C2 - 33689956
VL - 100
JO - EUR J CELL BIOL
JF - EUR J CELL BIOL
SN - 0171-9335
IS - 3
M1 - 151156
ER -
