ArticleCell death & disease2014
Erlotinib derivative inhibits hepatocellular carcinoma by targeting CIP2A to reactivate protein phosphatase 2A.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Association between gut microbiota and hepatocellular carcinoma from 2011 to 2022: Bibliometric analysis and global trends.Frontiers in oncology · 2023Pooled it
- The Emerging Role of the Cancerous Inhibitor of Protein Phosphatase 2A in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2025Review
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- ent-8(14),15-Pimaradiene-2β,19-diol, a diterpene from Aleuritopteris albofusca, inhibits growth and induces protective autophagy in hepatocellular carcinoma cells.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Biomarkers and Target-Specific Small-Molecule Drugs in Alzheimer's Diagnostic and Therapeutic Research: From Amyloidosis to Tauopathy.Neurochemical research · 2024Review
- Compound Taxus exerts marked anti-tumor activity and radiosensitization effect on hepatocellular carcinoma cells.Heliyon · 2024Article
- Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients.ACS omega · 2024Article
- CIP2A induces PKM2 tetramer formation and oxidative phosphorylation in non-small cell lung cancer.Cell discovery · 2024Article
- Altering phosphorylation in cancer through PP2A modifiers.Cancer cell international · 2024Review
- Alzheimer's Disease and Cancer: Common Targets.Mini reviews in medicinal chemistry · 2024Review
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- From Basic Science to Clinical Practice: The Role of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)/p90 in Cancer.Frontiers in genetics · 2023Review
- Strategies to target the cancer driver MYC in tumor cells.Frontiers in oncology · 2023Review
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Reciprocal regulation of CIP2A and AR expression in prostate cancer cells.Discover oncology · 2022Article
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- Identification of dynamic driver sets controlling phenotypical landscapes.Computational and structural biotechnology journal · 2022Article
- miR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1.Computational and mathematical methods in medicine · 2022Article
- The CIP2A-TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer.Nature cancer · 2021Article
- The effect ofJournal of gastrointestinal oncology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein phosphatase 2A (PP2A) is a tumor suppressor, which is functionally defective in various cancers. Previously, we found that PP2A activity determined the anticancer effect of bortezomib and erlotinib in hepatocellular carcinoma (HCC) cells. Here, we tested a novel erlotinib derivative, TD52, in four HCC cell lines, PLC5, Huh-7, Hep3B and Sk-Hep1. Using MTT and flow cytometry, we showed that TD52 had more potent apoptotic effects than erlotinib in HCC cells. TD52-induced apoptosis was associated with dose- and time- dependent reactivation of PP2A and downregulation of cancerous inhibitor of protein phosphatase 2A (CIP2A) and p-Akt. Inhibition of PP2A or ectopic expression of CIP2A or Akt in PLC5 cells abolished the effects of TD52. Furthermore, we demonstrated that TD52 affected the binding of Elk-1 to the proximal promoter of the CIP2A gene, thus downregulating transcription of CIP2A. Importantly, TD52-induced tumor inhibition was associated with reactivation of PP2A and downregulation of CIP2A and p-Akt in vivo. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A determines the apoptotic effect induced by TD52. Our findings disclose the therapeutic mechanism of this novel targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.
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