ArticleClinical and translational medicine2016
Targeting polo-like kinase 1, a regulator of p53, in the treatment of adrenocortical carcinoma.
Article in Clinical and translational medicine, 2016. 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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14 citing papers in PubMed, 31 citations in OpenAlex.
- Genomic Catastrophe Defines the Evolutionary Trajectory of Adrenocortical Carcinoma.Endocrine pathology · 2026Article
- An anoikis-based risk model predicts outcomes and is associated with the immune microenvironment in adrenocortical carcinoma.Frontiers in molecular biosciences · 2026Article
- A Senescence-Associated Gene Signature for Prognostic Prediction and Therapeutic Targeting in Adrenocortical Carcinoma.Biomedicines · 2025Article
- Therapeutic strategies for adrenocortical carcinoma: integrating genomic insights, molecular targeting, and immunotherapy.Frontiers in immunology · 2025Review
- PLK1 inhibitors as a new targeted treatment for adrenocortical carcinoma.Endocrine connections · 2024Article
- Advances in translational research of the rare cancer type adrenocortical carcinoma.Nature reviews. Cancer · 2023Review
- Article
- Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies.Endocrine reviews · 2022Article
- Nanoparticles-Based Strategies to Improve the Delivery of Therapeutic Small Interfering RNA in Precision Oncology.Pharmaceutics · 2022Review
- Inhibition of Polo-like Kinase 1 by HMN-214 Blocks Cell Cycle Progression and Inhibits Neuroblastoma Growth.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Antileukemia Effects of Notch-Mediated Inhibition of Oncogenic PLK1 in B-Cell Acute Lymphoblastic Leukemia.Molecular cancer therapeutics · 2019Article
- Targeted Assessment ofClinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- In vitro study of the Polo-like kinase 1 inhibitor volasertib in non-small-cell lung cancer reveals a role for the tumor suppressor p53.Molecular oncology · 2019Article
- Therapeutic Targets for Adrenocortical Carcinoma in the Genomics Era.Journal of the Endocrine Society · 2018Review
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8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundAdrenocortical carcinoma (ACC) is an aggressive cancer with a 5 year survival rate of 20-30 %. Various factors have been implicated in the pathogenesis of ACC including dysregulation of the G2/M transition and aberrant activity of p53 and MDM2. Polo-like kinase 1 (PLK-1) negatively modulates p53 functioning, promotes MDM2 activity through its phosphorylation, and is involved in the G2/M transition. Gene expression profiling of 44 ACC samples showed that increased expression of PLK-1 in 29 % of ACC. Consequently, we examined PLK-1's role in the modulation of the p53 signaling pathway in adrenocortical cancer.
methodsWe used siRNA knock down PLK-1 and pharmacological inhibition of PLK-1 and MDM2 ACC cell lines SW-13 and H295R. We examined viability, protein expression, p53 transactivation, and induction of apoptosis.
resultsKnocking down expression of PLK-1 with siRNA or inhibition of PLK-1 by a small molecule inhibitor, BI-2536, resulted in a loss of viability of up to 70 % in the ACC cell lines H295R and SW-13. In xenograft models, BI-2536 demonstrated marked inhibition of growth of SW-13 with less inhibition of H295R. BI-2536 treatment resulted in a decrease in mutant p53 protein in SW-13 cells but had no effect on wild-type p53 protein levels in H295R cells. Additionally, inhibition of PLK-1 restored wild-type p53's transactivation and apoptotic functions in H295R cells, while these functions of mutant p53 were restored only to a smaller extent. Furthermore, inhibition of MDM2 with nutlin-3 reduced the viability of both the ACC cells and also reactivated wild-type p53's apoptotic function. Inhibition of PLK-1 sensitized the ACC cell lines to MDM2 inhibition and this dual inhibition resulted in an additive apoptotic response in H295R cells with wild-type p53.
conclusionsThese preclinical studies suggest that targeting p53 through PLK-1 is an attractive chemotherapy strategy warranting further investigation in adrenocortical cancer.
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