ArticleClinical and translational medicine2021
Oncogenic PAX6 elicits CDK4/6 inhibitor resistance by epigenetically inactivating the LATS2-Hippo signaling pathway.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- β-ionone synergizes with 5-Fluorouracil to inhibit gastric cancer progression through PAX6-mediated cell cycle arrest.BMC cancer · 2026Article
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- UCHL3 depletion inhibits gastric cancer progression and enhances palbociclib sensitivity by regulating the AKT/CCND1 signaling axis via ENO1 ubiquitination.Cell death & disease · 2025Article
- Development of CDK4/6 Inhibitors in Gastrointestinal Cancers: Biomarkers to Move Forward.Current issues in molecular biology · 2025Review
- Nanosize Non-Viral Gene Therapy Reverses Senescence Reprograming Driven by PBRM1 Deficiency to Suppress iCCA Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells.Heliyon · 2025Article
- Nomogram model includingWorld journal of gastrointestinal surgery · 2024Article
- Review
- Inhibition of Eukaryotic Initiating Factor eIF4E Overcomes Abemaciclib Resistance in Gastric Cancer.Current medical science · 2023Article
- Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1.Cell death & disease · 2023Article
- PLAGL2 promotes bladder cancer progression via RACGAP1/RhoA GTPase/YAP1 signaling.Cell death & disease · 2023Article
- The Regulation of Cyclins and Cyclin-Dependent Kinases in the Development of Gastric Cancer.International journal of molecular sciences · 2023Review
- Article
- Oncogenic PAX6 elicits CDK4/6 inhibitor resistance by epigenetically inactivating the LATS2-Hippo signaling pathway.Clinical and translational medicine · 2021Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Intrinsic resistance to CDK4/6 inhibitors hinders their clinical utility in cancer treatment. Furthermore, the predictive markers of CDK4/6 inhibitors in gastric cancer (GC) remain incompletely described. Here, we found that PAX6 expression was negatively correlated with the response to palbociclib in vitro and in vivo in GC. We observed that the PAX6 expression level was negatively correlated with the overall survival of GC patients and further showed that PAX6 can promote GC cell proliferation and the cell cycle. The cell cycle is regulated by the interaction of cyclins with their partner serine/threonine cyclin-dependent kinases (CDKs), and the G1/S-phase transition is the main target of CDK4/6 inhibitors. Therefore, we tested whether PAX6 expression was correlated with the GC response to palbociclib. We found that PAX6 hypermethylates the promoter of LATS2 and inactivates the Hippo pathway, which upregulates cyclin D1 (CCND1) expression. This results in a suppressed response to palbociclib in GC. Furthermore, we found that the induction of the Hippo signaling pathway or treatment with a DNA methylation inhibitor could overcome PAX6-induced palbociclib resistance in GC. These findings uncover a tumor promoter function of PAX6 in GC and establish overexpressed PAX6 as a mechanism of resistance to palbociclib.
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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.