title: Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells.
abstract: 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.
authors.affiliation: 1] The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada [2] Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Cappello
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Blaser
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Gorrini
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, University Health Network, TMDT East Tower, MaRS Centre, Toronto, Ontario, Canada.
authors.forename: D C C
authors.initials: DC
authors.lastname: Lin
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
authors.forename: A J
authors.initials: AJ
authors.lastname: Elia
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Wakeham
authors.affiliation: Informatics and Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Haider
authors.affiliation: Informatics and Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: P C
authors.initials: PC
authors.lastname: Boutros
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, University Health Network, TMDT East Tower, MaRS Centre, Toronto, Ontario, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Mason
authors.affiliation: 1] Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: N A
authors.initials: NA
authors.lastname: Miller
authors.affiliation: 1] Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Youngson
authors.affiliation: 1] The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada [2] Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada [3] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: S J
authors.initials: SJ
authors.lastname: Done
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000473:pathology*; D020090:Chromosome Segregation / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D000072379:NIMA-Related Kinases; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*
chemical_list: C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; C490317:Nek2 protein, mouse; D017346:Protein Serine-Threonine Kinases