ArticleScientific reports2019
p27/Kip1 functions as a tumor suppressor and oncoprotein in osteosarcoma.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
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- Computer-aided discovery of CDK16 inhibitors: a docking-augmented machine learning regression modelling approach.Journal of computer-aided molecular design · 2026Article
- Astragalus mongholicus and Hedyotis diffusa willd inhibit cell proliferation by attenuating the miR-582-3p-p27 signaling pathway in LUAD.Scientific reports · 2025Article
- SAE1 promotes tumor cell malignancyActa pharmaceutica Sinica. B · 2025Article
- A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins.Cancers · 2025Review
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- Pivotal functions and impact of long con-coding RNAs on cellular processes and genome integrity.Journal of biomedical science · 2024Review
- The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.Clinical and translational medicine · 2024Review
- A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.Frontiers in immunology · 2024Review
- Emerging roles of cytosolic phosphoenolpyruvate kinase 1 (PCK1) in cancer.Biochemistry and biophysics reports · 2023Review
- StAR-related lipid transfer domain protein 3 (STARD3) regulates HER2 and promotes HER2-positive breast cancer progression through interaction with HSP90 and SRC signaling.American journal of cancer research · 2023Article
- FMNL2 suppresses cell migration and invasion of breast cancer: a reduction of cytoplasmic p27 via RhoA/LIMK/Cofilin pathway.Cell death discovery · 2022Article
- HAPLN1 confers multiple myeloma cell resistance to several classes of therapeutic drugs.PloS one · 2022Article
- Anti-Osteoclast Effect of Exportin-1 Inhibitor Eltanexor on Osteoporosis Depends on Nuclear Accumulation of IκBα-NF-κB p65 Complex.Frontiers in pharmacology · 2022Article
- Acetylshikonin, A Novel CYP2J2 Inhibitor, Induces Apoptosis in RCC Cells via FOXO3 Activation and ROS Elevation.Oxidative medicine and cellular longevity · 2022Article
- Therapeutic Targeting of Exportin-1 in Childhood Cancer.Cancers · 2021Review
- Characterization of Signalling Pathways That Link Apoptosis and Autophagy to Cell Death Induced by Estrone Analogues Which Reversibly Depolymerize Microtubules.Molecules (Basel, Switzerland) · 2021Article
- Acetylshikonin Induces Apoptosis in Human Colorectal Cancer HCT-15 and LoVo Cells via Nuclear Translocation of FOXO3 and ROS Level Elevation.Oxidative medicine and cellular longevity · 2021Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The p27/kip1 (p27) tumor suppressor inhibits cyclin/cyclin-dependent kinase (CDK) complexes and halts cell cycle progression. p27 further regulates invasion and migration in cancer cells, suggesting p27 also functions as an oncoprotein. Using a human osteosarcoma tissue microarray we identified high expression of cytoplasmic p27 in metastatic tumors. We demonstrated a positive correlation between mRNA and protein expression of p27 and expression of key metastatic markers, vimentin, snail-2, β-catenin and stathmin-1 (STMN1) in patient tumors. Our results show that T198 phosphorylation of p27 controls the interaction between p27 and STMN1 that regulates microtubule stabilization and the invasion and migration of osteosarcoma cells. We found that anti-tumoral activity of gemcitabine and the Wee1 kinase inhibitor AZD1775 in osteosarcoma cells, was dependent on drug sequencing that relied on p27 stabilization. Gemcitabine activated caspase-3 and synergized with AZD1775 through caspase-mediated cleavage of p27, that dissociated from STMN1 and effectively induced apoptosis. Further, blockage of nuclear export of p27 by inhibition of Exportin-1 (XPO1) promoted growth arrest, demonstrating that the biological effects of agents relied on the expression and localization of p27. Together, these data provide a rationale for combining chemotherapy with agents that promote p27 tumor suppressor activity for the treatment of osteosarcoma.
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