Ki-67 is required for maintenance of cancer stem cells but not cell proliferation

Justin Cidado, Hong Yuen Wong, D. Marc Rosen, Ashley Cimino-Mathews, Joseph P. Garay, Abigail G. Fessler, Zeshaan A. Rasheed, Jessica Hicks, Rory L. Cochran, Sarah Croessmann, Daniel J. Zabransky, Morassa Mohseni, Julia A. Beaver, David Chu, Karen Cravero, Eric S. Christenson, Arielle Medford, Austin Mattox, Angelo M. De Marzo, Pedram ArganiAjay Chawla, Paula J. Hurley, Josh Lauring, Ben Ho Park

Research output: Contribution to journalArticle

Abstract

Ki-67 expression is correlated with cell proliferation and is a prognostic marker for various cancers; however, its function is unknown. Here we demonstrate that genetic disruption of Ki-67 in human epithelial breast and colon cancer cells depletes the cancer stem cell niche. Ki-67 null cells had a proliferative disadvantage compared to wildtype controls in colony formation assays and displayed increased sensitivity to various chemotherapies. Ki-67 null cancer cells showed decreased and delayed tumor formation in xenograft assays, which was associated with a reduction in cancer stem cell markers. Immunohistochemical analyses of human breast cancers revealed that Ki-67 expression is maintained at equivalent or greater levels in metastatic sites of disease compared to matched primary tumors, suggesting that maintenance of Ki-67 expression is associated with metastatic/clonogenic potential. These results elucidate Ki-67's role in maintaining the cancer stem cell niche, which has potential diagnostic and therapeutic implications for human malignancies.

Original languageEnglish (US)
Pages (from-to)6281-6293
Number of pages13
JournalOncotarget
Volume7
Issue number5
DOIs
StatePublished - Jan 1 2016

Keywords

  • Cancer stem cells
  • Clonogenicity
  • Ki-67
  • Proliferation
  • Tumorigenicity

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Cidado, J., Wong, H. Y., Marc Rosen, D., Cimino-Mathews, A., Garay, J. P., Fessler, A. G., Rasheed, Z. A., Hicks, J., Cochran, R. L., Croessmann, S., Zabransky, D. J., Mohseni, M., Beaver, J. A., Chu, D., Cravero, K., Christenson, E. S., Medford, A., Mattox, A., De Marzo, A. M., ... Park, B. H. (2016). Ki-67 is required for maintenance of cancer stem cells but not cell proliferation. Oncotarget, 7(5), 6281-6293. https://doi.org/10.18632/oncotarget.7057