TY - JOUR
T1 - Disruption of Tacc3 function leads to in vivo tumor regression
AU - Yao, R.
AU - Natsume, Y.
AU - Saiki, Y.
AU - Shioya, H.
AU - Takeuchi, K.
AU - Yamori, T.
AU - Toki, H.
AU - Aoki, I.
AU - Saga, T.
AU - Noda, T.
PY - 2012/1/12
Y1 - 2012/1/12
N2 - 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.
AB - 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.
KW - TACC3
KW - mitosis
KW - p53
KW - spindle
KW - tumor regression
UR - http://www.scopus.com/inward/record.url?scp=84855776388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855776388&partnerID=8YFLogxK
U2 - 10.1038/onc.2011.235
DO - 10.1038/onc.2011.235
M3 - Article
C2 - 21685933
AN - SCOPUS:84855776388
VL - 31
SP - 135
EP - 148
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 2
ER -