KPT330 promotes the sensitivity of glioblastoma to olaparib by retaining SQSTM1 in the nucleus and disrupting lysosomal function

Autophagy. 2024 Feb;20(2):295-310. doi: 10.1080/15548627.2023.2252301. Epub 2023 Sep 15.

Abstract

AO: acridine orange; ATM: ATM serine/threonine kinase; CHEK1: checkpoint kinase 1; CHEK2: checkpoint kinase 2; CI: combination index; DMSO: dimethyl sulfoxide; DSBs: double-strand breaks; GBM: glioblastoma; HR: homologous recombination; H2AX: H2A.X variant histone; IHC: immunohistochemistry; LAPTM4B: lysosomal protein transmembrane 4 beta; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PARP: poly(ADP-ribose) polymerase; RAD51: RAD51 recombinase; SQSTM1: sequestosome 1; SSBs: single-strand breaks; RNF168: ring finger protein 168; XPO1: exportin 1.

Keywords: Autophagic flux; KPT330; SQSTM1; glioblastoma; lysosome; olaparib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy
  • Glioblastoma*
  • Humans
  • Membrane Proteins / metabolism
  • Oncogene Proteins / metabolism
  • Phthalazines / pharmacology
  • Piperazines*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proteins / metabolism
  • Sequestosome-1 Protein / metabolism
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • olaparib
  • Sequestosome-1 Protein
  • Phthalazines
  • Proteins
  • Poly(ADP-ribose) Polymerases
  • SQSTM1 protein, human
  • LAPTM4B protein, human
  • Membrane Proteins
  • Oncogene Proteins
  • RNF168 protein, human
  • Ubiquitin-Protein Ligases
  • Piperazines