ArticleOncogenesis2018
Targeted reduction of the EGFR protein, but not inhibition of its kinase activity, induces mitophagy and death of cancer cells through activation of mTORC2 and Akt.
Article in Oncogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
25 citing papers in PubMed, 57 citations in OpenAlex.
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- Pyrazoline B Induces Oxidative Stress Mediated Toxicity, Cell Cycle Arrest, and Caspase-Independent Apoptosis in BT-474 Human Breast Cancer Cells.Journal of experimental pharmacology · 2025Article
- Unleashing the power of peptides in prostate cancer immunotherapy: mechanism, facts and perspectives.Frontiers in pharmacology · 2025Review
- Mitophagy in gynecological malignancies: roles, advances, and therapeutic potential.Cell death discovery · 2024Review
- CYpHER: catalytic extracellular targeted protein degradation with high potency and durable effect.Nature communications · 2024Article
- Article
- Drug resistance‑related gene targets and molecular mechanisms in the A2780/Taxol‑resistant epithelial ovarian cancer cell line.Oncology letters · 2024Article
- CYpHER: Catalytic extracellular targeted protein degradation with high potency and durable effect.bioRxiv : the preprint server for biology · 2024Article
- Comprehensive analyses of mitophagy-related genes and mitophagy-related lncRNAs for patients with ovarian cancer.BMC women's health · 2024Article
- Mitophagy genes in ovarian cancer: a comprehensive analysis for improved immunotherapy.Discover oncology · 2023Article
- Unraveling the Peculiar Features of Mitochondrial Metabolism and Dynamics in Prostate Cancer.Cancers · 2023Review
- GABP couples oncogene signaling to telomere regulation in TERT promoter mutant cancer.Cell reports · 2022Article
- Mitophagy-mediated molecular subtypes depict the hallmarks of the tumour metabolism and guide precision chemotherapy in pancreatic adenocarcinoma.Frontiers in cell and developmental biology · 2022Article
- The Mechanism of Osthole in the Treatment of Gastric Cancer Based on Network Pharmacology and Molecular Docking Technology.Applied bionics and biomechanics · 2022Article
- Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR.Cancers · 2021Article
- Tyrosine kinase-independent actions of DDR2 in tumor cells and cancer-associated fibroblasts influence tumor invasion, migration and metastasis.Journal of cell science · 2021Article
- A rotamer relay information system in the epidermal growth factor receptor-drug complexes reveals clues to new paradigm in protein conformational change.Computational and structural biotechnology journal · 2021Article
- Mitophagy promotes sorafenib resistance through hypoxia-inducible ATAD3A dependent Axis.Journal of experimental & clinical cancer research : CR · 2020Article
- Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer.Aging · 2020Article
- Targeting the non-canonical roles of PCNA modifies and increases the response to targeted anti-cancer therapy.Oncotarget · 2019Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The oncogenic epidermal growth factor receptor (EGFR) is commonly overexpressed in solid cancers. The tyrosine kinase activity of EGFR has been a major therapeutic target for cancer; however, the efficacy of EGFR tyrosine kinase inhibitors to treat cancers has been challenged by innate and acquired resistance at the clinic. Accumulating evidence suggests that EGFR possesses kinase-independent pro-survival functions, and that cancer cells are more vulnerable to reduction of EGFR protein than to inhibition of its kinase activity. The molecular mechanism underlying loss-of-EGFR-induced cell death remains largely unknown. In this study, we show that, unlike inhibiting EGFR kinase activity that is known to induce pro-survival non-selective autophagy, downregulating EGFR protein, either by siRNA, or by a synthetic EGFR-downregulating peptide (Herdegradin), kills prostate and ovarian cancer cells via selective mitophagy by activating the mTORC2/Akt axis. Furthermore, Herdegradin induced mitophagy and inhibited the growth of orthotopic ovarian cancers in mice. This study identifies anti-mitophagy as a kinase-independent function of EGFR, reveals a novel function of mTORC2/Akt axis in promoting mitophagy in cancer cells, and offers a novel approach for pharmacological downregulation of EGFR protein as a potential treatment for EGFR-positive cancers.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.