Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells

• Published in: Oncogene Vol. 33; no. 18; pp. 2375 - 2384
• Main Authors: Cappello, P, Blaser, H, Gorrini, C, Lin, D C C, Elia, A J, Wakeham, A, Haider, S, Boutros, P C, Mason, J M, Miller, N A, Youngson, B, Done, S J, Mak, T W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2014; Nature Publishing Group
• Subjects: 631/80/128/1965; 692/420/2489/1381/1286; 692/699/67/1347; 692/700/1750; Aneuploidy; Animals; Apoptosis; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer research; Cancer therapies; Cell Biology; Cell cycle; Cell death; Cell Line, Tumor; Centrosome - pathology; Chromosome Segregation - genetics; Cytoskeleton; Development and progression; Female; Gene Knockdown Techniques; Gene regulation; Genetic aspects; Human Genetics; Humans; Internal Medicine; Kinases; Lung Neoplasms - secondary; Mammary gland; Medicine; Medicine & Public Health; Metastases; Metastasis; Mice; Neoplasm Transplantation; NIMA-Related Kinases; Oncology; original-article; Phosphotransferases; Physiological aspects; Protein kinase; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - physiology; Risk factors; Solid tumors; Therapeutic targets; Tumor cell lines; Tumor cells; Tumorigenesis; Canada; aneuploidy; breast cancer; kinase; cell death; cell cycle; metastasis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2013.183

Breast cancer is the most common solid tumor and the second most common cause of death in women. Despite a large body of literature and progress in breast cancer research, many molecular aspects of this complex disease are still poorly understood, hindering the design of specific and effective therapeutic strategies. To identify the molecules important in breast cancer progression and metastasis, we tested the
in vivo
effects of inhibiting the functions of various kinases and genes involved in the regulation/modulation of the cytoskeleton by downregulating them in mouse PyMT mammary tumor cells and human breast cancer cell lines. These kinases and cytoskeletal regulators were selected based on their prognostic values for breast cancer patient survival. PyMT tumor cells, in which a selected gene was stably knocked down were injected into the tail veins of mice, and the formation of tumors in the lungs was monitored. One of the several genes found to be important for tumor growth in the lungs was NIMA-related kinases 2 (
Nek2
), a cell cycle-related protein kinase. Furthermore, Nek2 was also important for tumor growth in the mammary fat pad. In various human breast cancer cell lines, Nek2 knockdown induced aneuploidy and cell cycle arrest that led to cell death. Significantly, the breast cancer cell line most sensitive to Nek2 depletion was of the triple negative breast cancer subtype. Our data indicate that Nek2 has a pivotal role in breast cancer growth at primary and secondary sites, and thus may be an attractive and novel therapeutic target for this disease.