A phenotypic screen identifies microtubule plus end assembly regulators that can function in mitotic spindle orientation

Stolz, Ailine; Ertych, Norman; Bastians, Holger

doi:10.1080/15384101.2014.1000693

Cited by 26 publications

(31 citation statements)

References 25 publications

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“…24,25 Evidence also exists showing that APC, together with EB1, might control some parameters of microtubule plus end dynamics, 24 but microtubule plus end growth is not influenced by EB1 and APC per se. 26 In addition to that, APC can also form complexes with spindle assembly checkpoint proteins such as Bub1 and Bub3 suggesting that APC might also be involved in the regulation of the mitotic spindle assembly checkpoint. 25 However, details about this possible regulation have not been reported yet.…”

Section: Additional Functions Of Wnt Pathway Components During Mitosismentioning

confidence: 99%

Fresh WNT into the regulation of mitosis

Stolz

Bastians

2015

Cell Cycle

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Section: Additional Functions Of Wnt Pathway Components During Mitosismentioning

confidence: 99%

Fresh WNT into the regulation of mitosis

Stolz

Bastians

2015

Cell Cycle

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“…Indeed, decreased ch‐TOG expression in cells is known to reduce MT assembly rates in mitotic spindles (Ertych et al, ). There are other pathways that can increase spindle MT assembly rates in addition to the ch‐TOG pathway (Stolz, Ertych, & Bastians, ) and we are presently investigating which alternate pathway is impacted upon GPR124 depletion. In accordance with GPR124 overexpression, simply increasing ch‐TOG expression in HCT116 cells, which have been extensively characterized with regard to MT assembly and express moderate levels of GPR124 (Figure S1; Ertych et al, ), enhanced spindle MT assembly by 22% ( p = 0.001; Figure S4).…”

Section: Resultsmentioning

confidence: 99%

GPR124 regulates microtubule assembly, mitotic progression, and glioblastoma cell proliferation

Cherry

Vicente

et al. 2019

Glia

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GPR124 is involved in embryonic development and remains expressed by select organs. The importance of GPR124 during development suggests that its aberrant expression might participate in tumor growth. Here we show that both increases and decreases in GPR124 expression in glioblastoma cells reduce cell proliferation by differentially altering the duration mitotic progression. Using mass spectrometry‐based proteomics, we discovered that GPR124 interacts with ch‐TOG, a known regulator of both microtubule (MT)‐plus‐end assembly and mitotic progression. Accordingly, changes in GPR124 expression and ch‐TOG similarly affect MT assembly measured by real‐time microscopy in cells. Our study describes a novel molecular interaction involving GPR124 and ch‐TOG at the plasma membrane that controls glioblastoma cell proliferation by modifying MT assembly rates and controlling the progression of distinct phases of mitosis.

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“…To test whether elevated MT dynamics was causative for CIN in HGSC we treated cells with a low dose of the MT stabilising agent, taxol, previously demonstrated to suppress MT assembly rates in colorectal cancer 9 . To first establish whether low dose taxol could suppress elevated MT assembly rates in HGSC, we took advantage of an proxy read out: monopolar mitotic spindles frequently orient asymmetrically when MT assembly is elevated 42 (Figure 3i). Using this assay, we confirmed that low dose taxol treatment reduced MT assembly rates in HGSC cell lines (Figure 3i, j).…”

Section: Supernumerary Centrosomes and Aberrant Mt Dynamics Contributmentioning

confidence: 99%

Mechanisms of Chromosomal Instability in High-grade Serous Ovarian Carcinoma

Tamura

Shaikh

Muliaditan

et al. 2019

Preprint

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Chromosomal instability (CIN), the continual gain and loss of chromosomes or parts of chromosomes, occurs in the majority of cancers and confers poor prognosis. Mechanisms driving CIN remain unknown in most cancer types due to a scarcity of functional studies.High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, is the major cause of death due to gynaecological malignancy in the Western world with chemotherapy resistance developing in almost all patients. HGSC exhibits high rates of chromosome aberrations and knowledge of causative mechanisms is likely to represent an important step towards combating the poor prognosis of this disease. However, very little is known about the nature of chromosomal instability exhibited by this cancer type in particular due to a historical lack of appropriate cell line models. Here we perform the first in-depth functional characterisation of mechanisms driving CIN in HGSC by analysing eight cell lines that accurately recapitulate HGSC genetics as defined by recent studies. We show, using a range of established functional CIN assays combined with live cell imaging and single molecule DNA fibre analysis, that multiple mechanisms co-exist to drive CIN in HGSC.These include supernumerary centrosomes, elevated microtubule dynamics and DNA replication stress. By contrast, the spindle assembly checkpoint was intact. These findings are relevant for developing therapeutic approaches to manipulating CIN in ovarian cancer, and suggests that such approaches may need to be multimodal to combat multiple co-existing CIN drivers.

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A phenotypic screen identifies microtubule plus end assembly regulators that can function in mitotic spindle orientation

Cited by 26 publications

References 25 publications

Fresh WNT into the regulation of mitosis

Fresh WNT into the regulation of mitosis

GPR124 regulates microtubule assembly, mitotic progression, and glioblastoma cell proliferation

Mechanisms of Chromosomal Instability in High-grade Serous Ovarian Carcinoma

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