ArticleOncotarget2017
Activation of cancerous inhibitor of PP2A (CIP2A) contributes to lapatinib resistance through induction of CIP2A-Akt feedback loop in ErbB2-positive breast cancer cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- The Emerging Role of the Cancerous Inhibitor of Protein Phosphatase 2A in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2025Review
- Targeting the TRIB3-MYC axis in cancer: mechanistic insights and therapeutic disruption strategies.Investigational new drugs · 2025Review
- Cancerous Inhibitor of Phosphatase 2A (CIP2A): A Sensitive Diagnostic Marker and Therapeutic Agent in Oral Cancer.Current medicinal chemistry · 2025Article
- PP2A activation overcomes leptomeningeal dissemination in group 3 medulloblastoma.The Journal of biological chemistry · 2024Article
- CIP2A as a Key Regulator for AKT Phosphorylation Has Partial Impact Determining Clinical Outcome in Breast Cancer.Journal of clinical medicine · 2022Article
- Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy.American journal of cancer research · 2021Review
- PP2A: A Promising Biomarker and Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
- Anti-cancer Drug Response Prediction Using Neighbor-Based Collaborative Filtering with Global Effect Removal.Molecular therapy. Nucleic acids · 2018Article
- A Hybrid Interpolation Weighted Collaborative Filtering Method for Anti-cancer Drug Response Prediction.Frontiers in pharmacology · 2018Article
- PP2A as the Main Node of Therapeutic Strategies and Resistance Reversal in Triple-Negative Breast Cancer.Molecules (Basel, Switzerland) · 2017Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Lapatinib, a small molecule ErbB2/EGFR inhibitor, is FDA-approved for the treatment of metastatic ErbB2-overexpressing breast cancer; however, lapatinib resistance is an emerging clinical challenge. Understanding the molecular mechanisms of lapatinib-mediated anti-cancer activities and identifying relevant resistance factors are of pivotal significance. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that is overexpressed in breast cancer. Our study investigated the role of CIP2A in the anti-cancer efficacy of lapatinib in ErbB2-overexpressing breast cancer cells. We found that lapatinib concurrently downregulated CIP2A and receptor tyrosine kinase signaling in ErbB2-overexpressing SKBR3 and 78617 cells; however, these effects were attenuated in lapatinib-resistant (LR) cells. CIP2A overexpression rendered SKBR3 and 78617 cells resistant to lapatinib-induced apoptosis and growth inhibition. Conversely, CIP2A knockdown via lentiviral shRNA enhanced cell sensitivity to lapatinib-induced growth inhibition and apoptosis. Results also suggested that lapatinib downregulated CIP2A through regulation of protein stability. We further demonstrated that lapatinib-induced CIP2A downregulation can be recapitulated by LY294002, suggesting that Akt mediates CIP2A upregulation. Importantly, lapatinib induced differential CIP2A downregulation between parental BT474 and BT474/LR cell lines. Moreover, CIP2A shRNA knockdown significantly sensitized the BT474/LR cells to lapatinib. Collectively, our results demonstrate that CIP2A is a molecular target and resistance factor of lapatinib with a critical role in lapatinib-induced cellular responses, including the inhibition of the CIP2A-Akt feedback loop. Further investigation of lapatinib-mediated CIP2A regulation will advance our understanding of lapatinib-associated anti-tumor activities and drug resistance.
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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.