State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518039, China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Cell Death Dis. 2018 Jan 22;9(2):72. doi: 10.1038/s41419-017-0112-6.
Accumulating evidence has shown that transforming acidic coiled-coil 3 (TACC3) is deregulated in a broad spectrum of cancers. In the present study, we reported that TACC3 was markedly elevated in bladder cancer, especially in muscle-invasive bladder cancers (MIBCs). The upregulation of TACC3 was positively associated with tumor invasiveness, grade, T stage, and progression in patients with bladder cancer. Furthermore, a Kaplan-Meier survival analysis showed that patients with bladder cancer whose tumors had high TACC3 expression experienced a dismal prognosis compared with patients whose tumors had low TACC3 expression. Functional studies have found that TACC3 is a prerequisite for the development of malignant characteristics of bladder cancer cells, including cell proliferation and invasion. Moreover, TACC3 promoted G1/S transition, which was mediated via activation of the transcription of E2F1, eventually enhancing cell proliferation. Notably, the overexpression of TACC3 or E2F1 indicates a high sensitivity to cisplatin. Taken together, these findings define a tumor-supportive role for TACC3, which may also serve as a prognostic and therapeutic indicator in bladder cancers.
越来越多的证据表明，转化酸性卷曲螺旋 3（TACC3）在广泛的癌症中失调。在本研究中，我们报道 TACC3 在膀胱癌中明显升高，尤其是在肌层浸润性膀胱癌（MIBC）中。TACC3 的上调与膀胱癌患者的肿瘤侵袭性、分级、T 分期和进展呈正相关。此外，Kaplan-Meier 生存分析表明，TACC3 表达水平高的膀胱癌患者的预后比 TACC3 表达水平低的患者差。功能研究发现，TACC3 是膀胱癌细胞恶性特征发展的必要条件，包括细胞增殖和侵袭。此外，TACC3 通过激活 E2F1 的转录促进 G1/S 期过渡，最终增强细胞增殖。值得注意的是，TACC3 或 E2F1 的过表达表明对顺铂高度敏感。总之，这些发现定义了 TACC3 的肿瘤支持作用，它也可能作为膀胱癌的预后和治疗指标。
