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Disruption of Tacc3 function leads to in vivo tumor regression | Oncogene
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The formation of the bipolar spindle is responsible for accurate chromosomal segregation during mitosis. The dynamic instability of microtubules has an important role in this process, and has been shown to be an effective target for cancer chemotherapy. Several agents that target non-microtubule mitotic proteins, including the motor protein Eg5, Aurora kinases and Polo-like kinases, are currently being developed as chemotherapeutic drugs. However, because the efficacies of these drugs remain elusive, new molecular targets that have essential roles in tumor cells are desired. Here, we provide in vivo evidence that transforming acidic coiled-coil-3 (Tacc3) is a potential target for cancer chemotherapy. Using MRI, we showed that Tacc3 loss led to the regression of mouse thymic lymphoma in vivo, which was accompanied by massive apoptosis. By contrast, normal tissues, including the thymus, showed no overt abnormalities, despite high Tacc3 expression. in vitro analysis indicated that Tacc3 depletion induced multi-polar spindle formation, which led to mitotic arrest, followed by apoptosis. Similar responses have been observed in Burkitt
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nature portfolio permissions reprints privacy policy nature 445 nature advertising social media paclitaxel-induced cell death transforming acidic coiled-coil-3 transforming acidic coiled-coil cancer research spindle-dependent chromosome alignment small-cell lung cancer personal data centrosomal protein d-tacc fission yeast alp14/tog author correspondence ch-tog/xmap215 protein springerlink instant access centrosome-dependent microtubule assembly data protection tacc-ling microtubule dynamics permissions normal development advanced development drosophila meiotic spindles tacc3 depletion sensitizes human disease models chronic lymphocytic leukemia spindle cell features privacy supplementary figure s2 supplementary figure s3 supplementary figure s4 supplementary figure s5 supplementary figure s6 p53-mutant mice tacc domain identifies small molecules degrading lymphoma cell lines spindle pole organization centrosome amplification motor protein eg5 ch-tog/xmap215 centrosomal protein tacc3 highly conserved regions development explore content subscription content bipolar spindle formation
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