title: Kinesin-5 Contributes to Spindle-length Scaling in the Evolution of Cancer toward Metastasis.
abstract: During natural evolution, the spindles often scale with cell sizes to orchestrate accurate chromosome segregation. Whether in cancer evolution, when the constraints on genome integrity are relaxed, cancer cells may evolve the spindle to confer other advantages has not been investigated. Using invasion as a selective pressure in vitro, we found that a highly metastatic cancer clone displays a lengthened metaphase spindle, with faster spindle elongation that correlates with transiently elevated speed of cell migration. We found that kinesin-5 is upregulated in this malignant clone, and weak inhibition of kinesin-5 activity could revert the spindle to a smaller aspect ratio, decrease the speed of spindle pole separation, and suppress post-mitotic cell migration. A correlation was found between high aspect ratio and strong metastatic potential in cancers that evolved and were selected in vivo, implicating that the spindle aspect ratio could serve as a promising cellular biomarker for metastatic cancer clones.
authors: Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.
authors: Ching-Feng
authors: CF
authors: Yang
authors: Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.
authors: Wan-Yu
authors: WY
authors: Tsai
authors: Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.
authors: Wei-An
authors: WA
authors: Chen
authors: Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan.
authors: Kai-Wen
authors: KW
authors: Liang
authors: Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.
authors: Cheng-Ju
authors: CJ
authors: Pan
authors: Genome and Systems Biology Degree Program, National Taiwan University, Taipei 10617, Taiwan.
authors: Pei-Lun
authors: PL
authors: Lai
authors: Department of Internal Medicine, National Taiwan University, Taipei 10617, Taiwan.
authors: Pan-Chyr
authors: PC
authors: Yang
authors: Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.|Genome and Systems Biology Degree Program, National Taiwan University, Taipei 10617, Taiwan.|Department of Life Science, National Taiwan University, Taipei 10617, Taiwan.|Graduate Institute of Electronics Engineering, National Taiwan University, Taipei 10617, Taiwan.
authors: Hsiao-Chun
authors: HC
authors: Huang
mesh_terms: D005075:Biological Evolution; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D048429:Cell Size; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000473:pathology / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016547:Kinesins