Deleting key autophagy elongation proteins induces acquirement of tumor-associated phenotypes via ISG15

Eun Bin Kong, Hag Dong Kim, Joon Kim

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Autophagy is a cellular catabolic process that maintains intracellular homeostasis using lysosomal degradation systems. We demonstrate that inhibiting autophagy by depleting essential autophagy elongation proteins, Atg5 or Atg7, induces ISG15 expression through STING-mediated cytosolic dsDNA response. Genome stability is impaired in ATG5- or ATG7-depleted cells, and thus, double-strand breakages of DNA increase and cytosolic dsDNA accumulates. Accumulated cytosolic dsDNA induces the STING pathway to activate type I IFN signals which induce STAT1 activity and downregulate ATF3. When depletion of ATG5 or ATG7 inhibits autophagy, ATF3 is downregulated and STAT1 is upregulated. Furthermore, inhibiting autophagy induces ISG15 expression through STAT1 activation, which promotes acquisition of tumor-associated phenotypes such as migration, invasion, and proliferation. In conclusion, it appears that via the STING-mediated cytosolic dsDNA response, the STAT1-ISG15 axis mediates the relationship between autophagy and the immune system in relation to tumor progression. Moreover, combined with autophagy control, regulating ISG15 expression could be a novel strategy for cancer immunotherapy.

Original languageEnglish
Pages (from-to)2517-2530
Number of pages14
JournalCell Death and Differentiation
Volume27
Issue number8
DOIs
Publication statusPublished - 2020 Aug 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Deleting key autophagy elongation proteins induces acquirement of tumor-associated phenotypes via ISG15'. Together they form a unique fingerprint.

Cite this