Defective autophagy associated with LC3 puncta in epothilone-resistant cancer cells

Si Shen, Oliver Kepp, Isabelle Martins, Ilio Vitale, Sylvie Souquère, Maria Castedo, Gérard Pierron, Guido Kroemer

Research output: Contribution to journalArticle

Abstract

Autophagy is commonly characterized by the redistribution of the microtubule-associated light chain 3 (LC3) protein into cytoplasmic puncta, coinciding with its lipidation, as well as by a decrease in the abundance of autophagic substrates including p62 and ubiquitinylated proteins. Here, we describe a cell line, A549-B480, which, in contrast to its parental A549 line, exhibits massive accumulation of LC3 (or a GFP-LC3 fusion protein) in cytoplasmic puncta. These puncta co-localize with accumulated p62 and ubiquitinylated proteins, yet are not enwrapped by membranes. Indeed, LC3 is not lipidated in A549-B480, even when these cells are cultured in conditions in which A549 cells would develop autophagy. A549-B480 cells have been selected for their resistance against the microtubule-stabilizing agent epothilone B and actually require the continuous presence of epothilone B for their survival. Parental A549 cells treated with epothilone B manifested all signs of bona fide autophagy. In contrast, the autophagic program of A549-B480 was defective, irrespective of the absence or presence of epothilone B, and correlated with the complete absence of Atg7, a protein that is reputed to be essential for autophagy. These results establish novel functional links between microtubules and autophagy, identify a new chemotherapy resistance-associated autophagic defect, and describe the existence of LC3 puncta outside from autophagosomes.

Original languageEnglish
Pages (from-to)377-383
Number of pages7
JournalCell Cycle
Volume9
Issue number2
DOIs
Publication statusPublished - Jan 15 2010

Keywords

  • Apoptosis
  • Autophagy
  • Chemotherapy
  • Epothilone B
  • Fibrillar aggregates

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Defective autophagy associated with LC3 puncta in epothilone-resistant cancer cells'. Together they form a unique fingerprint.

  • Cite this

    Shen, S., Kepp, O., Martins, I., Vitale, I., Souquère, S., Castedo, M., Pierron, G., & Kroemer, G. (2010). Defective autophagy associated with LC3 puncta in epothilone-resistant cancer cells. Cell Cycle, 9(2), 377-383. https://doi.org/10.4161/cc.9.2.10468