ArticleOncogene2014
A small compound targeting TACC3 revealed its different spatiotemporal contributions for spindle assembly in cancer cells.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Transforming acidic coiled-coil-containing protein 3-mediated lipid metabolism reprogramming impairs CD8Signal transduction and targeted therapy · 2025Article
- Pathogenic variants of TUBB8 cause oocyte spindle defects by disrupting with EB1/CAKP5 interactions and potential treatment targeting microtubule acetylation through HDAC6 inhibition.Clinical and translational medicine · 2025Article
- Targeting TACC3 Induces Immunogenic Cell Death and Enhances T-DM1 Response in HER2-Positive Breast Cancer.Cancer research · 2024Article
- TPX2 Amplification-Driven Aberrant Mitosis in Culture Adapted Human Embryonic Stem Cells with gain of 20q11.21.Stem cell reviews and reports · 2023Article
- Centrosome-dependent microtubule modifications set the conditions for axon formation.Cell reports · 2022Article
- Review
- Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer.Cancer science · 2021Article
- Dual Inhibition of γ-Tubulin and Plk1 Induces Mitotic Cell Death.Frontiers in pharmacology · 2020Article
- Targeting centrosome amplification, an Achilles' heel of cancer.Biochemical Society transactions · 2019Review
- Elevated Expression of Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3) Is Associated With a Poor Prognosis in Osteosarcoma.Clinical orthopaedics and related research · 2018Article
- A small compound spindlactone A sensitizes human endometrial cancer cells to TRAIL-induced apoptosis via the inhibition of NAD(P)H dehydrogenase quinone 1.OncoTargets and therapy · 2018Article
- SNIPER(TACC3) induces cytoplasmic vacuolization and sensitizes cancer cells to Bortezomib.Cancer science · 2017Article
- Article
- Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival.Scientific reports · 2016Article
- Genomic insights into head and neck cancer.Cancers of the head & neck · 2016Article
- High expression of TACC3 in esophageal squamous cell carcinoma correlates with poor prognosis.Oncotarget · 2015Article
- MAPping the Ndc80 loop in cancer: A possible link between Ndc80/Hec1 overproduction and cancer formation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2015Review
- TACC3 protein regulates microtubule nucleation by affecting γ-tubulin ring complexes.The Journal of biological chemistry · 2014Article
- Cancer cell death induced by novel small molecules degrading the TACC3 protein via the ubiquitin-proteasome pathway.Cell death & disease · 2014Article
- Targeting Alp7/TACC to the spindle pole body is essential for mitotic spindle assembly in fission yeast.FEBS letters · 2014Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitotic spindle is assembled by the coordinated action of centrosomes and kinetochore microtubules. An evolutionally conserved protein family, transforming acidic coiled-coil (TACC), has been shown to be involved in this process. In humans, TACC3 is aberrantly expressed in a variety of human cancers, but its biological significance remains to be elucidated. Here, using a novel compound targeting TACC3, spindlactone (SPL), we show that the perturbation of TACC3 selectively inhibited the nucleation of centrosome microtubules in ovarian cancer cells. In contrast to centrosome microtubules, the kinetochore microtubules were robustly assembled, forming ectopic spindle poles that resulted in multipolar spindles. Interestingly, the extensive inhibition of TACC3 partially suppressed the nucleation of kinetochore microtubules. These dose-dependent effects of SPL were consistent with the results observed by the depletion of TACC3 and its binding partner, colonic and hepatic tumor overexpressed gene protein (TOGp). Although these proteins both have roles in the assembly of centrosome and kinetochore microtubules, their contributions were spatiotemporally different. Notably, SPL did not affect spindle assembly in normal cells. Furthermore, the oral administration of SPL significantly suppressed tumor growth in vivo. The unique mechanism of action of SPL not only enables it to be used as a tool to dissect the molecular basis of spindle assembly but also to provide a rationale for the use of TACC3 as a molecular target for cancer treatment. This rationale offers an opportunity to develop new strategies for cancer chemotherapy that overcome the limitations of microtubule toxins and expand their scope and clinical efficacy.
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