TACC3 transcriptionally upregulates E2F1 to promote cell growth and confer sensitivity to cisplatin in bladder cancer

Zhi-Rui Lin,Meng-Yao Wang,Wei-Ren Huang,Shi-Yang He,Zhi-Ming Cai

doi:10.1038/s41419-017-0112-6

Abstract

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

Highlights

According to the latest cancer statistics, bladder cancer is the ninth most-common cancer worldwide and the fourth major cause of morbidity and mortality in men[1]
We noticed that the muscle-invasive bladder cancers (MIBCs) subtype exhibited a more profound increase in transforming acidic coiled-coil protein 3 (TACC3) expression among the four different patient cohorts examined[14,23,26,27,28] (Fig. 1g, h), which clearly indicated that the activation of TACC3 might be a crucial genetic event in the development or progression to MIBC
As a member of a family of three related proteins with highly conserved C-terminal coiled-coil domains, TACC3 is necessary for organization of mitotic spindle formation, which is required for proper chromosome segregation during cell division

Summary

Introduction

According to the latest cancer statistics, bladder cancer is the ninth most-common cancer worldwide and the fourth major cause of morbidity and mortality in men[1]. In China, the incidence rate of bladder cancer has continued to rise. Bladder cancers are considered either low-grade non-muscle-invasive bladder cancers (superficial or NMIBCs), which account for 70% of tumor occurrence, or high-grade muscle-invasive bladder cancers (invasive or MIBCs), which are responsible for the majority of bladder cancer-specific deaths. Its 5-year survival rate is around 90%, NMIBCs are. The transforming acidic coiled-coil protein 3 (TACC3) protein belongs to the TACC family of centrosomal proteins with a highly conserved C-terminal coiled-coil domain[4]. TACC3 is one of the essential regulators of mitotic progression and functions via the promotion of microtubule (MT) stability during the assembly of mitotic spindle in mammals[5,6,7,8].

Methods

Results

Conclusion