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Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
08:29

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel

Published on: May 14, 2018

TACC3 depletion sensitizes to paclitaxel-induced cell death and overrides p21WAF-mediated cell cycle arrest

L Schneider1, F Essmann, A Kletke

  • 1Institut für Biochemie und Molekularbiologie II, Universitätsklinikum der Heinrich-Heine-Universität, Düsseldorf, Germany.

Oncogene
|June 30, 2007
PubMed

Insights

Transforming acidic coiled coil (TACC) 3 depletion causes cell cycle arrest but enhances paclitaxel-induced apoptosis. TACC3 is a potential target to overcome p21(WAF)-associated resistance to chemotherapy.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Mitotic spindle regulators are key targets for cancer therapy.
  • Transforming acidic coiled coil (TACC) 3 is crucial for spindle assembly and chromosome segregation.

Purpose of the Study:

  • To investigate the role of TACC3 in mitotic progression and its impact on chemotherapy response.
  • To determine if TACC3 can be targeted to enhance the efficacy of antitumor agents like paclitaxel.

Main Methods:

  • Inducible RNA interference was used to downregulate TACC3 expression in NIH3T3 fibroblasts.
  • Cell cycle progression, ploidy, apoptosis, and signaling pathways (p53-p21(WAF), Akt) were analyzed.
  • TACC3-depleted and proficient cells were treated with paclitaxel.

Main Results:

  • TACC3 knockdown induced aneuploidy and a reversible cell cycle arrest via the p53-p21(WAF) pathway.
  • Paclitaxel induced polyploidy and apoptosis in TACC3-depleted cells, unlike in TACC3-proficient cells.
  • TACC3 depletion abrogated paclitaxel-induced survival signaling (Akt, cytoplasmic p21(WAF), cyclin D1), leading to cell death.

Conclusions:

  • TACC3 plays a role in protecting cancer cells from paclitaxel-induced apoptosis.
  • Targeting TACC3 may overcome p21(WAF)-mediated resistance to paclitaxel in antitumor therapy.

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