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- Title
Kif18A is involved in human breast carcinogenesis.
- Authors
Chunpeng Zhang; Changjun Zhu; Hongyan Chen; Linwei Li; Linwei Guo; Wei Jiang; Shih Hsin Lu
- 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.
- Subjects
BREAST cancer; CANCER cell growth; MICROTUBULES; KINESIN; CANCER invasiveness
- Publication
Carcinogenesis, 2010, Vol 31, Issue 9, p1676
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgq134