ArticleJournal of cellular physiology2020
Neratinib degrades MST4 via autophagy that reduces membrane stiffness and is essential for the inactivation of PI3K, ERK1/2, and YAP/TAZ signaling.
Article in Journal of cellular physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03919292 (Phase 1/2 Study of Neratinib and Divalproex Sodium), which is not on this map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase 1/2 Study of Neratinib and Divalproex Sodium (Valproate) in Advanced Solid Tumors, With an Expansion Cohort in Ras-Mutated Cancers
Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- The MST4-14-3-3ζ complex promotes pancreatic cancer by activating YAP.Biology direct · 2026Article
- The SCD1 inhibitor aramchol interacts with regorafenib and metformin to kill tumor cells.Oncotarget · 2026Article
- Potential repurposing of lapatinib and pazopanib as neuroprotective agents in a rat model of Huntington's disease.Inflammopharmacology · 2025Article
- GZ17-6.02 kills PDX isolates of uveal melanoma.Oncotarget · 2024Article
- The mammalian Sterile 20-like kinase 4 (MST4) signaling in tumor progression: Implications for therapy.Cancer letters · 2023Review
- The role of irreversible pan-HER tyrosine kinase inhibitors in the treatment of HER2-Positive metastatic breast cancer.Frontiers in pharmacology · 2023Review
- Article
- KRAS: A Druggable Target in Colon Cancer Patients.International journal of molecular sciences · 2022Review
- Neratinib kills B-RAF V600E melanoma via ROS-dependent autophagosome formation and death receptor signaling.Pigment cell & melanoma research · 2022Article
- Osimertinib-resistant NSCLC cells activate ERBB2 and YAP/TAZ and are killed by neratinib.Biochemical pharmacology · 2021Article
- Article
- Review
- MST4 negatively regulates the EMT, invasion and metastasis of HCC cells by inactivating PI3K/AKT/Snail1 axis.Journal of Cancer · 2021Article
- GZ17-6.02 and Pemetrexed Interact to Kill Osimertinib-Resistant NSCLC Cells That Express Mutant ERBB1 Proteins.Frontiers in oncology · 2021Article
- GZ17-6.02 Interacts With [MEK1/2 and B-RAF Inhibitors] to Kill Melanoma Cells.Frontiers in oncology · 2021Article
- AR12 (OSU-03012) suppresses GRP78 expression and inhibits SARS-CoV-2 replication.Biochemical pharmacology · 2020Article
- Review
- Emerging role of the Hippo pathway in autophagy.Cell death & disease · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The irreversible ERBB1/2/4 inhibitor neratinib causes plasma membrane-associated K-RAS to mislocalize into intracellular vesicles liminal to the plasma membrane; this effect is enhanced by HDAC inhibitors and is now a Phase I trial (NCT03919292). The combination of neratinib and HDAC inhibitors killed pancreatic cancer and lymphoma T cells. Neratinib plus HDAC inhibitor exposure was as efficacious as (paclitaxel+gemcitabine) at killing pancreatic cancer cells. Neratinib reduced the phosphorylation of PAK1, Merlin, LATS1/2, AKT, mTOR, p70 S6K, and ERK1/2 which required expression of Rubicon, Beclin1, and Merlin. Neratinib altered pancreatic tumor cell morphology which was associated with MST4 degradation reduced Ezrin phosphorylation and enhanced phosphorylation of MAP4K4 and LATS1/2. Knockdown of the MAP4K4 activator and sensor of membrane rigidity RAP2A reduced basal LATS1/2 and YAP phosphorylation but did not prevent neratinib from stimulating LATS1/2 or YAP phosphorylation. Beclin1 knockdown prevented MST4 degradation, Ezrin dephosphorylation and neratinib-induced alterations in tumor cell morphology. Our findings demonstrate that neratinib enhances LATS1/2 phosphorylation independently of RAP2A/MAP4K4 and that MST4 degradation and Ezrin dephosphorylation may represent a universal trigger for the biological actions of neratinib.
Indexed as
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.