ArticleOncotarget2015
PP2A inhibitors arrest G2/M transition through JNK/Sp1- dependent down-regulation of CDK1 and autophagy-dependent up-regulation of p21.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
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- Combination of dasatinib and okadaic acid induces apoptosis and cell cycle arrest by targeting protein phosphatase PP2A in chronic myeloid leukemia cells.Medical oncology (Northwood, London, England) · 2022Article
- Chinese Herbal Medicine for Primary Liver Cancer Therapy: Perspectives and Challenges.Frontiers in pharmacology · 2022Review
- Anticancer Attributes of Cantharidin: Involved Molecular Mechanisms and Pathways.Molecules (Basel, Switzerland) · 2020Review
- Tanshinone I induces apoptosis and protective autophagy in human glioblastoma cells via a reactive oxygen species‑dependent pathway.International journal of molecular medicine · 2020Article
- PP2A: A Promising Biomarker and Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
- The combination of cantharidin and antiangiogenic therapeutics presents additive antitumor effects against pancreatic cancer.Oncogenesis · 2018Article
- JNK and Yorkie drive tumor progression by generating polyploid giant cells in Drosophila.Oncogene · 2018Article
- LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells.International journal of molecular medicine · 2018Article
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- The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells.Oncotarget · 2017Article
- NCTD promotes Birinapant-mediated anticancer activity in breast cancer cells by downregulation of c-FLIP.Oncotarget · 2017Article
- Aloperine Protects Mice against DSS-Induced Colitis by PP2A-Mediated PI3K/Akt/mTOR Signaling Suppression.Mediators of inflammation · 2017Article
- Cantharidin Overcomes Imatinib Resistance by Depleting BCR-ABL in Chronic Myeloid Leukemia.Molecules and cells · 2016Article
- The ER stress regulator Bip mediates cadmium-induced autophagy and neuronal senescence.Scientific reports · 2016Article
- Therapeutic relevance of the protein phosphatase 2A in cancer.Oncotarget · 2016Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Protein phosphatase 2A (PP2A) plays an important role in the control of the cell cycle. We previously reported that the PP2A inhibitors, cantharidin and okadaic acid (OA), efficiently repressed the growth of cancer cells. In the present study, we found that PP2A inhibitors arrested the cell cycle at the G2 phase through a mechanism that was dependent on the JNK pathway. Microarrays further showed that PP2A inhibitors induced expression changes in multiple genes that participate in cell cycle transition. To verify whether these expression changes were executed in a PP2A-dependent manner, we targeted the PP2A catalytic subunit (PP2Ac) using siRNA and evaluated gene expression with a microarray. After the cross comparison of these microarray data, we identified that CDK1 was potentially the same target when treated with either PP2A inhibitors or PP2Ac siRNA. In addition, we found that the down-regulation of CDK1 occurred in a JNK-dependent manner. Luciferase reporter gene assays demonstrated that repression of the transcription of CDK1 was executed through the JNK-dependent activation of the Sp1 transcription factor. By constructing deletion mutants of the CDK1 promoter and by using ChIP assays, we identified an element in the CDK1 promoter that responded to the JNK/Sp1 pathway after stimulation with PP2A inhibitors. Cantharidin and OA also up-regulated the expression of p21, an inhibitor of CDK1, via autophagy rather than PP2A/JNK pathway. Thus, this present study found that the PP2A/JNK/Sp1/CDK1 pathway and the autophagy/p21 pathway participated in G2/M cell cycle arrest triggered by PP2A inhibitors.
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