ArticleCell death & disease2024
Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- VCP at the crossroads of UPS and autophagy in cancer.Genes & diseases · 2027Review
- Organelle contact reorganization drives calcium-dependent autophagy under proteostatic stress.Autophagy · 2026Article
- Scaling covalent ligand discovery through dynamic combinatorial library-versus-proteome screening.Nature communications · 2026Article
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- A cyclometalated iridium(III) complex induces paraptotic cell death via mitochondrial dysfunction and ER stress in triple-negative breast cancer cells.Frontiers in pharmacology · 2026Article
- MLKL/retromer axis controls PD-L1 recycling to compromise antitumor immunity during VCP inhibition-induced necroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- High VCP/p97 expression associates with low PD-L1 TPS in oropharyngeal squamous cell carcinoma.Discover oncology · 2025Article
- Potent Inducers of Paraptosis through Electronic Tuning of Hemicyanine Electrophiles.Journal of the American Chemical Society · 2025Article
- Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics.Cancers · 2025Review
- Nigericin Induces Paraptosis-Like Cell Death Instead of Pyroptosis in Corneal Keratocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- SHP2-mediated ROS activation induces chondrocyte paraptosis in osteoarthritis and is attenuated by low-intensity pulsed ultrasound.Journal of orthopaedic translation · 2025Article
- Dysregulated ribosome quality control in human diseases.The FEBS journal · 2025Review
- Valosin containing protein (VCP/p97) expression in laryngeal squamous cell carcinoma: clinical evaluation and implications for targeted therapy.Pathology oncology research : POR · 2025Article
- Exploring paraptosis as a therapeutic approach in cancer treatment.Journal of biomedical science · 2024Review
- Natural products-induced cancer cell paraptosis.Food science & nutrition · 2024Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Valosin-containing protein (VCP)/p97, an AAA+ ATPase critical for maintaining proteostasis, emerges as a promising target for cancer therapy. This study reveals that targeting VCP selectively eliminates breast cancer cells while sparing non-transformed cells by inducing paraptosis, a non-apoptotic cell death mechanism characterized by endoplasmic reticulum and mitochondria dilation. Intriguingly, oncogenic HRas sensitizes non-transformed cells to VCP inhibition-mediated paraptosis. The susceptibility of cancer cells to VCP inhibition is attributed to the non-attenuation and recovery of protein synthesis under proteotoxic stress. Mechanistically, mTORC2/Akt activation and eIF3d-dependent translation contribute to translational rebound and amplification of proteotoxic stress. Furthermore, the ATF4/DDIT4 axis augments VCP inhibition-mediated paraptosis by activating Akt. Given that hyperactive Akt counteracts chemotherapeutic-induced apoptosis, VCP inhibition presents a promising therapeutic avenue to exploit Akt-associated vulnerabilities in cancer cells by triggering paraptosis while safeguarding normal cells.
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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 Socratic graph.