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Disruption of Tacc3 function leads to in vivo tumor regression

Oncogene volume 31, pages 135–148 (2012)Cite this article

Abstract

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's lymphoma and T-ALL. These results show that Tacc3 is a vulnerable component of the spindle assembly in lymphoma cells and is a promising cancer chemotherapy target.

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Acknowledgements

We thank T Jacks for providing the R26CreERT2 mice; S Shibata, T Nakahara T Shimomura, S Saito and F Yamagishi for MRI imaging; S Hasegawa for helpful discussions; and Y Terui for the donation of human lymphoma cells. We also thank Y Inoue and T Hirota for critically reading the manuscript. This work was supported by a Grant-in-Aid for cancer research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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  1. Y Saiki

    Present address: 6Current address: Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.,

Authors and Affiliations

  1. Department of Cell Biology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo, Japan

    R Yao, Y Natsume, Y Saiki, H Shioya & T Noda

  2. Department of Pathology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo, Japan

    K Takeuchi

  3. Division of Molecular Pharmacology, Cancer Chemotherapy Center, The Japanese Foundation for Cancer Research, Tokyo, Japan

    T Yamori

  4. Team for Advanced Development and Evaluation of Human Disease Models, Bioresource Center, RIKEN, Ibaraki, Japan

    H Toki & T Noda

  5. Diagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Science, Chiba, Japan

    I Aoki & T Saga

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Correspondence to R Yao.

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Yao, R., Natsume, Y., Saiki, Y. et al. Disruption of Tacc3 function leads to in vivo tumor regression. Oncogene 31, 135–148 (2012). https://doi.org/10.1038/onc.2011.235

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