The mitotic tensegrity guardian tau protects mammary epithelia from katanin-like1-induced aneuploidy

Haruka Sudo, Kazunori Nakajima

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The microtubule associated-protein tau has been identified as an effective positive prognostic indicator in breast cancer. To explore the physiological function of tau in early carcinogenesis, endogenous tau was knocked down in primary cultured human mammary epithelial cells. This resulted in chromosome-bridging during anaphase followed by micronucleation, both of which were suppressed by a further kataninlike1 knockdown. We also detected that the exogenously expressed katanin-like1 induction of cellular transformation is prevented by exogenous tau in rat fibroblasts. The mutant katanin-like1 (L123V) identified in breast cancer showed an increase in this transformation capacity as well as microtubule severing activity resistant to tau. The tau knockdown resulted in a loss of the kinetochore fibers on which tau is normally localized. This physical fragility was also observed in isolated tauknockdown mitotic spindles, supporting the relevance of microtubule damage to the onset of transformation. The karyotyping of tau-knockdown cells showed increased frequency of loss of one X chromosome, further suggesting the involvement of tau in breast tumorigenesis. We propose that tau may contribute to tumor progression by protecting spindle microtubules from excess severing by katanin-like1. We also present data indicating that the microtubule-binding octapeptide NAP is a candidate modifier against the tau deficiency in tumor cells.

Original languageEnglish
Pages (from-to)53712-53734
Number of pages23
JournalOncotarget
Volume7
Issue number33
DOIs
Publication statusPublished - 2016 Aug 1

Keywords

  • Breast cancer
  • Chromosome instability
  • Microtubule severing
  • Mitotic spindle
  • Tau

ASJC Scopus subject areas

  • Oncology

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