ArticlePloS one2014
Autophagosome-mediated EGFR down-regulation induced by the CK2 inhibitor enhances the efficacy of EGFR-TKI on EGFR-mutant lung cancer cells with resistance by T790M.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- CK2 and the Hallmarks of Cancer.Biomedicines · 2022Review
- Essential role for STAT3/FOXM1/ATG7 signaling-dependent autophagy in resistance to Icotinib.Journal of experimental & clinical cancer research : CR · 2022Article
- Role of PARP1-mediated autophagy in EGFR-TKI resistance in non-small cell lung cancer.Scientific reports · 2020Article
- Studies of Non-Protective Autophagy Provide Evidence that Recovery from Therapy-Induced Senescence is Independent of Early Autophagy.International journal of molecular sciences · 2020Article
- Protein Kinase CK2 in Cancer Energetics.Frontiers in oncology · 2020Review
- Quinalizarin, a specific CK2 inhibitor, can reduce icotinib resistance in human lung adenocarcinoma cell lines.International journal of molecular medicine · 2019Article
- Role of protein kinase CK2 in antitumor drug resistance.Journal of experimental & clinical cancer research : CR · 2019Review
- Opportunities and challenges of co-targeting epidermal growth factor receptor and autophagy signaling in non-small cell lung cancer.Oncology letters · 2019Review
- CX-4945 Induces Methuosis in Cholangiocarcinoma Cell Lines by a CK2-Independent Mechanism.Cancers · 2018Article
- Cell death-based treatment of lung adenocarcinoma.Cell death & disease · 2018Review
- CAGE Binds to Beclin1, Regulates Autophagic Flux and CAGE-Derived Peptide Confers Sensitivity to Anti-cancer Drugs in Non-small Cell Lung Cancer Cells.Frontiers in oncology · 2018Article
- Interplay of autophagy, receptor tyrosine kinase signalling and endocytic trafficking.Essays in biochemistry · 2017Review
- Protein kinase CK2 is important for the function of glioblastoma brain tumor initiating cells.Journal of neuro-oncology · 2017Article
- EGFR Family Members' Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer.Cancers · 2017Review
- Differential protein stability of EGFR mutants determines responsiveness to tyrosine kinase inhibitors.Oncotarget · 2016Article
- Autophagy is not uniformly cytoprotective: a personalized medicine approach for autophagy inhibition as a therapeutic strategy in non-small cell lung cancer.Biochimica et biophysica acta · 2016Review
- Protein kinase CK2 in breast cancer: the CK2β regulatory subunit takes center stage in epithelial plasticity.Cellular and molecular life sciences : CMLS · 2015Review
- Article
Corrections and comments
- Expression of concern · 2019-03-14Duplication of/in Image · Manipulation of Images ·
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinase CK2 has diverse functions promoting and maintaining cancer phenotypes. We investigated the effect of CK2 inhibition in lung cancer cells with T790M-mediated resistance to the EGFR-TK inhibitor. Resistant sublines of PC-9 to gefitinib (PC-9/GR) and erlotinib (PC-9/ER) were established by previous study, and T790M secondary mutation was found in both resistant sublines. A decrease of EGFR by siRNA treatment effectively controlled the growth of resistant cells, thus suggesting that they still have EGFR-dependency. CX-4945, a potent and selective CK2 inhibitor, induced autophagy in PC-9/GR and PC-9/ER, and which was supported by the induction of autophagic vacuoles and microtubule-associated protein 1 light chain 3 (LC3) expression, and the increase of punctate fluorescent signals in resistant cells pre-transfected with green fluorescent protein (GFP)-tagged LC3. However, the withdrawal of CX-4945 led to the recovery of cancer cells with autophagy. We found that the induction of autophagy by CX-4945 in both resistant cells was CK2 dependent by using small interfering RNA against CK2. The treatment with CX-4945 alone induced a minimal growth inhibition in resistant cells. However, combined treatment of CX-4945 and EGFR-TKI effectively inhibited cancer-cell proliferation and induced apoptosis. CX-4945 increased the translocation of EGFR from the cell surface into the autophagosome, subsequently leading to the decrease of EGFR while inhibition of autophagy by 3MA or Atg7-targeted siRNA pretreatment reduced the decrease of EGFR by CX-4945. Accordingly, apoptosis by a combination of CX-4945 and EGFR-TKI was suppressed by 3MA or Atg7-targeted siRNA pretreatment, thus suggesting that autophagosome-mediated EGFR down-regulation would have an important role regarding apoptotic cell death by EGFR-TKI. Combined treatment of the CK2 inhibitor and EGFR-TKI may be a promising strategy for overcoming T790M-mediated resistance.
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