Zeb1-mediated autophagy enhances resistance of breast cancer cells to genotoxic drugs

Olga Fedorova, Alexandra Daks, Sergey Parfenyev, Oleg Shuvalov, Sofia Netsvetay, Julia Vasileva, Anastasia Gudovich, Vasilii Golotin, Oleg Semenov, Alexey Petukhov, Ekaterina Baiduik, Nurken Berdigaliyev, Eugene M. Tulchinsky, Nikolai A. Barlev

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Autophagy is a highly conserved process of cellular self-digestion that involves the formation of autophagosomes for the delivery of intracellular components and dysfunctional organelles to lysosomes. This process is induced by different signals including starvation, mitochondrial dysfunction, and DNA damage. The molecular link between autophagy and DNA damage is not well understood yet. Importantly, tumor cells utilize the mechanism of autophagy to cope with genotoxic anti-cancer drug therapy. Another mechanism of drug resistance is provided to cancer cells via the execution of the EMT program. One of the critical transcription factors of EMT is Zeb1. Here we demonstrate that Zeb1 is involved in the regulation of autophagy in several breast cancer cell models. On the molecular level, Zeb1 likely facilitates autophagy through the regulation of autophagic genes, resulting in increased LC3-II levels, augmented staining with Lysotracker, and increased resistance to several genotoxic drugs. The attenuation of Zeb1 expression in TNBC cells led to the opposite effect. Consequently, we propose that Zeb1 augments the resistance of breast cancer cells to genotoxic drugs, at least partially, via autophagy. Collectively, we have uncovered a novel function of Zeb1 in the regulation of autophagy in breast cancer cells.

Original languageEnglish
Pages (from-to)29-34
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume589
DOIs
Publication statusPublished - Jan 22 2022

Keywords

  • Anticancer therapy
  • Autophagy
  • EMT
  • p53
  • Zeb1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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