Journal Article

Kif18A is involved in human breast carcinogenesis

Chunpeng Zhang, Changjun Zhu, Hongyan Chen, Linwei Li, Liping Guo, Wei Jiang and Shih Hsin Lu

in Carcinogenesis

Volume 31, issue 9, pages 1676-1684
Published in print September 2010 | ISSN: 0143-3334
Published online July 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq134
Kif18A is involved in human breast carcinogenesis

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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.

Journal Article.  6247 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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