Anti-ZW10 polyclonal antibody

Background: ZW10 binding factor (ZWINT) has been reported to be upregulated in various human cancers and predict worse survival. However, the expression profile, clinical significance, and biological role of ZWINT remains unclear in breast cancer. Material/Methods: In this study, we investigated messenger RNA (mRNA) and protein expression levels of ZWINT in breast cancer tissues, and the prognostic value of ZWINT protein expression was validated in a cohort of breast cancer patients using immunohistochemistry analysis. Then, different bioinformatic analyses were combined to explore the potential cancer-related hallmark underlying ZWINT in breast cancer, and a series of experiments in vitro were performed to reveal the oncogenic role of ZWINT in breast cancer. Results: Significant upregulation of ZWINT was observed in breast cancer tissues compared to normal and para-tumor tissues and upregulation of ZWINT predicts poor prognosis in breast cancer patients. Additionally, ZWINT could promote breast cancer proliferation via cell cycle regulation, especially by influencing the expression of some critical cell cycle regulators involved in G1 phase and G1/S transition. Finally, miR-204 was identified as a tumor suppressor microRNA which directly targets a specific site in 3'-UTR of ZWINT. Conclusions: Overall, our results indicated that miR-204/ZWINT/cell cycle process might play an important role in breast cancer progression.

Mitotic spindle formation and chromosome segregation depend critically on kinetochore-microtubule (KT-MT) interactions. A new protein, termed Spindly in Drosophila and SPDL-1 in C. elegans, was recently shown to regulate KT localization of dynein, but depletion phenotypes revealed striking differences, suggesting evolutionarily diverse roles of mitotic dynein. By characterizing the function of Spindly in human cells, we identify specific functions for KT dynein. We show that localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B. hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment. Moreover, depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein. However, in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs. Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation.