Technical Reference #3129

3129.

Kif18A is involved in human breast carcinogenesis Chunpeng Zhang; Changjun Zhu; Hongyan Chen; Linwei Li; Liping Guo; Wei Jiang; and Shih Hsin Lu, Chinese Academy of Medical Sciences, Carcinogenesis, 31(3129), (2010)
Link To Paper

Abstract:
Microtubule (MT) kinesin motor proteins orchestrate various cellular processes (e.g. mitosis motility and organelle transportation) and have been implicated in human carcinogenesis. Kif18A a plus-end directed MT depolymerase kinesin regulates MT dynamics chromosome congression and cell division. In this study we report that Kif18A is overexpressed in human breast cancers and Kif18A overexpression is associated with tumor grade metastasis and poor survival. Functional analyses reveal that ectopic overexpression of Kif18A results in cell multinucleation whereas ablation of Kif18A expression significantly inhibits the proliferative capability of breast cancer cells in vitro and in vivo. Inhibition of Kif18A not only affects the critical mitotic function of Kif18A but also decreases cancer cell migration by stabilizing MTs at leading edges and ultimately induces anoikis of cells with inactivation of the phosphatidylinositol 3-kinase–Akt signaling pathway. Together our results indicate that Kif18A is involved in human breast carcinogenesis and may serve as a potential therapeutic target for human breast cancer.

Materials & Methods:
Time-lapse microscopy Time-lapse microscopy was performed as described previously (19). In brief HeLa cells stably expressed yellow fluorescent protein-tubulin or EB1–GFP fusion proteins were grown on a 35 mm poly-lysine coated glass bottom microwell dish (MatTek Ashland MA) for 24 h and then transfected with Luciferase

Microscopic Technique
Time-lapse microscopy

Cell Type(s)
HeLa Cells