title: Disruption of Tacc3 function leads to in vivo tumor regression.
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.
authors.affiliation: Department of Cell Biology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo, Japan. ryao@jfcr.or.jp
authors.forename: R
authors.initials: R
authors.lastname: Yao
authors.forename: Y
authors.initials: Y
authors.lastname: Natsume
authors.forename: Y
authors.initials: Y
authors.lastname: Saiki
authors.forename: H
authors.initials: H
authors.lastname: Shioya
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Yamori
authors.forename: H
authors.initials: H
authors.lastname: Toki
authors.forename: I
authors.initials: I
authors.lastname: Aoki
authors.forename: T
authors.initials: T
authors.lastname: Saga
authors.forename: T
authors.initials: T
authors.lastname: Noda
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D005326:Fetal Proteins / Q000235:genetics / Q000502:physiology*; D016158:Genes, p53; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008869:Microtubule-Associated Proteins; D009365:Neoplasm Regression, Spontaneous / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*; D013953:Thymus Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D002352:Carrier Proteins; D005326:Fetal Proteins; D008869:Microtubule-Associated Proteins; C418485:TACC3 protein, mouse