ArticleOncogene2020
Therapeutic targeting of the PI4K2A/PKR lysosome network is critical for misfolded protein clearance and survival in cancer cells.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- xinguangA preliminary characterization of PI4K/PIPK alterations across solid tumors: an exploratory framework for prognostic and therapeutic stratification.Cancer biology & therapy · 2026Article
- PI4K and PIPK families in breast cancer: subtype-specific oncogenic mechanisms and precision therapeutic strategies.Molecular biology reports · 2026Review
- Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.Nature communications · 2026Article
- Phosphatidylinositol 4-kinase α suppresses glioblastoma progression by inactivating YAP and PI3K/Akt signaling.The Journal of biological chemistry · 2026Article
- Lysosomal quality control Review.Autophagy · 2025Review
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Lysosomal Repair in Health and Disease.Journal of cellular physiology · 2025Review
- Bystanders or active players: the role of extra centrosomes as signaling hubs.Cancer metastasis reviews · 2024Review
- Exosomal misfolded proteins released by cancer stem cells: dual functions in balancing protein homeostasis and orchestrating tumor progression.Discover oncology · 2024Review
- Picornavirus security proteins promote the release of extracellular vesicle enclosed viruses via the modulation of host kinases.PLoS pathogens · 2024Article
- Review
- A Plethora of Functions Condensed into Tiny Phospholipids: The Story of PI4P and PI(4,5)PCells · 2023Review
- EMT-activated secretory and endocytic vesicular trafficking programs underlie a vulnerability to PI4K2A antagonism in lung cancer.The Journal of clinical investigation · 2023Article
- Canonical and Noncanonical ER Stress-Mediated Autophagy Is a Bite the Bullet in View of Cancer Therapy.Cells · 2022Review
- Microarray data reveal potential genes that regulate triple-negative breast cancer.The Journal of international medical research · 2022Article
- CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR.Journal of hematology & oncology · 2022Article
- Identifying key genes in milk fat metabolism by weighted gene co-expression network analysis.Scientific reports · 2022Article
- pH Sensitive Dextran Coated Fluorescent Nanodiamonds as a Biomarker for HeLa Cells Endocytic Pathway and Increased Cellular Uptake.Nanomaterials (Basel, Switzerland) · 2021Article
- Article
- Tumor Necrosis Factor α Reduces SNAP29 Dependent Autolysosome Formation to Increase Prion Protein Level and Promote Tumor Cell Migration.Virologica Sinica · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The role of RNA-dependent protein kinase R (PKR) and its association with misfolded protein expression in cancer cells are unclear. Herein we report that PKR regulates misfolded protein clearance by preventing it release through exosomes and promoting lysosomal degradation of misfolded prion proteins in cancer cells. We demonstrated that PKR contributes to the lysosome function and regulates misfolded prion protein clearance. We hypothesized that PKR-associated lysosome function is critical for cancer but not normal cell survival, representing an effective approach for highly targeted cancer therapy. In screening a compound library, we identified two PKR-associated compounds 1 and 2 (Pac 1 and 2) did not affect normal cells but selectively induced cell death in cancer cells depending on their PKR expression status. Pac 1 significantly inhibited the growth of human lung and breast xenograft tumors in mice with no toxicity. Pac 1 binds to PI4K2A and disrupts the PKR/PI4K2A-associated lysosome complex, contributing to destabilization of cancer cell lysosomes and triggering cell death. We observed that PKR and PI4K2A play significant prognostic roles in breast cancer patients. These results demonstrate that targeting of a PI4K2A/PKR lysosome complex may be an effective approach for cancer therapy.
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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.