ArticleCancer research2013
Chk1 targeting reactivates PP2A tumor suppressor activity in cancer cells.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Succinylation of tumor suppressor PPP2R1A K541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling to display oncogene function.Acta pharmaceutica Sinica. B · 2025Article
- The Emerging Role of the Cancerous Inhibitor of Protein Phosphatase 2A in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2025Review
- Nuclear compression-mediated DNA damage drives ATR-dependent Lamin expression and mouse ESC differentiation.Nucleic acids research · 2025Article
- From Basic Science to Clinical Practice: The Role of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)/p90 in Cancer.Frontiers in genetics · 2023Review
- Chk1 Inhibition Ameliorates Alzheimer's Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- CIP2A Interacts with TopBP1 and Drives Basal-Like Breast Cancer Tumorigenesis.Cancer research · 2021Article
- CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress.Molecular cell · 2020Article
- CIP2A-promoted astrogliosis induces AD-like synaptic degeneration and cognitive deficits.Neurobiology of aging · 2019Article
- Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth.Translational oncology · 2019Article
- PP2A: A Promising Biomarker and Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
- CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing increased apoptosis in bladder cancer cells.Oncology reports · 2018Article
- Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate: Implications for priming of neuroblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer's Disease.Cell reports · 2018Article
- Targeting of epigenetic regulators in neuroblastoma.Experimental & molecular medicine · 2018Review
- HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130.Nature communications · 2018Article
- 11q deletion in neuroblastoma: a review of biological and clinical implications.Molecular cancer · 2017Review
- Article
- The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation.Nucleic acids research · 2017Article
- High expression of CIP2A protein is associated with tumor aggressiveness in stage I-III NSCLC and correlates with poor prognosis.OncoTargets and therapy · 2017Article
- CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
Checkpoint kinase Chk1 is constitutively active in many cancer cell types and new generation Chk1 inhibitors show marked antitumor activity as single agents. Here we present a hitherto unrecognized mechanism that contributes to the response of cancer cells to Chk1-targeted therapy. Inhibiting chronic Chk1 activity in cancer cells induced the tumor suppressor activity of protein phosphatase protein phosphatase 2A (PP2A), which by dephosphorylating MYC serine 62, inhibited MYC activity and impaired cancer cell survival. Mechanistic investigations revealed that Chk1 inhibition activated PP2A by decreasing the transcription of cancerous inhibitor of PP2A (CIP2A), a chief inhibitor of PP2A activity. Inhibition of cancer cell clonogenicity by Chk1 inhibition could be rescued in vitro either by exogenous expression of CIP2A or by blocking the CIP2A-regulated PP2A complex. Chk1-mediated CIP2A regulation was extended in tumor models dependent on either Chk1 or CIP2A. The clinical relevance of CIP2A as a Chk1 effector protein was validated in several human cancer types, including neuroblastoma, where CIP2A was identified as an NMYC-independent prognostic factor. Because the Chk1-CIP2A-PP2A pathway is driven by DNA-PK activity, functioning regardless of p53 or ATM/ATR status, our results offer explanative power for understanding how Chk1 inhibitors mediate single-agent anticancer efficacy. Furthermore, they define CIP2A-PP2A status in cancer cells as a pharmacodynamic marker for their response to Chk1-targeted therapy.
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