Involvement of autophagy in the outcome of mitotic catastrophe

Irina V Sorokina1, Tatiana V Denisenko1, Gabriela Imreh2,3

  • 1Faculty of Fundamental Medicine, MV Lomonosov Moscow State University, 11999, Moscow, Russia.

Scientific Reports
|November 8, 2017
PubMed

Insights

Tumor cells evade death through mitotic catastrophe (MC), a process involving autophagy and apoptosis. Mitochondria regulate this balance, with proteins like Mcl-1 and Bcl-xL influencing cell fate decisions.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Research

Background:

  • Tumor progression is driven by evasion of cell death, a significant challenge in cancer research.
  • Mitotic catastrophe (MC) is a cell death pathway that can compromise therapeutic resistance.
  • Understanding MC is crucial for developing effective cancer treatments.

Purpose of the Study:

  • To investigate the role of autophagy and apoptosis in MC-induced cell death.
  • To explore the function of mitochondria-linked anti-apoptotic proteins in MC.
  • To elucidate the interplay between MC, autophagy, and apoptosis in cancer cells.

Main Methods:

  • Induction of MC in colorectal and non-small cell lung carcinoma cell lines.
  • Utilizing Atg13 knockout and Mcl-1/Bcl-xL overexpression models.
  • Analyzing the rates of MC, autophagy, and apoptosis.

Main Results:

  • MC induction in colorectal cancer cells triggers autophagy followed by apoptosis.
  • Autophagy suppression significantly reduces MC rates in lung cancer cells.
  • Mitochondria-associated proteins Mcl-1 and Bcl-xL modulate MC duration and the autophagy-apoptosis balance.

Conclusions:

  • MC is a critical decision point for cell death, with mitochondria regulating the balance between MC, autophagy, and apoptosis.
  • Targeting Mcl-1 and Bcl-xL may offer therapeutic strategies by influencing MC and cell death pathways.
  • Autophagy plays a key role in the progression of MC-induced cell death.

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