ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
Cytoplasmic sequestration of p27 via AKT phosphorylation in renal cell carcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- p27Histology and histopathology · 2025Pooled it
- Suppression of neuronal p27 impairs cognitive function in middle-aged mice.Neurobiology of disease · 2026Article
- A Spatiotemporal Model of CXCL10 as a Master Regulator of Immune Evasion and Metastasis in Osteosarcoma.International journal of molecular sciences · 2025Review
- Review
- Regulation of p27 (Kip1) by Ubiquitin E3 Ligase RNF6.Pharmaceutics · 2022Article
- Down regulation of fatty acid synthaseCurrent research in pharmacology and drug discovery · 2022Article
- Clear cell renal cell carcinoma ontogeny and mechanisms of lethality.Nature reviews. Nephrology · 2021Review
- Chronic Sulforaphane Administration Inhibits Resistance to the mTOR-Inhibitor Everolimus in Bladder Cancer Cells.International journal of molecular sciences · 2020Article
- Mislocalized cytoplasmic p27 activates PAK1-mediated metastasis and is a prognostic factor in osteosarcoma.Molecular oncology · 2020Article
- Microenvironment-Derived FGF-2 Stimulates Renal Cell Carcinoma Cell Proliferation through Modulation of p27Kip1: Implications for Spatial Niche Formation and Functional Intratumoral Heterogeneity.Pathobiology : journal of immunopathology, molecular and cellular biology · 2020Article
- Targeted therapy of the AKT kinase inhibits esophageal squamous cell carcinoma growth in vitro and in vivo.International journal of cancer · 2019Article
- Peroxisome Proliferator Activated Receptor Gamma Sensitizes Non-small Cell Lung Carcinoma to Gamma Irradiation Induced Apoptosis.Frontiers in genetics · 2019Article
- Metastatic Renal Cell Cancer-Systemic Therapy.Indian journal of surgical oncology · 2018Article
- Article
- Quantitative Systems Biology to decipher design principles of a dynamic cell cycle network: the "Maximum Allowable mammalian Trade-Off-Weight" (MAmTOW).NPJ systems biology and applications · 2017Review
- Target molecule expression profiles in metastatic renal cell carcinoma: Development of individual targeted therapy.Tissue engineering and regenerative medicine · 2016Article
- Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma.Oncogene · 2016Article
- Association of cytoplasmic p27 expression with an unfavorable response to cisplatin-based chemotherapy and poor outcomes in non-small cell lung cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Autophagy and Apoptotic Crosstalk: Mechanism of Therapeutic Resistance in HER2-Positive Breast Cancer.Breast cancer : basic and clinical research · 2016Review
- Resistance to Antiangiogenic Therapy Is Associated with an Immunosuppressive Tumor Microenvironment in Metastatic Renal Cell Carcinoma.Cancer immunology research · 2015Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
purposep27 localization and expression has prognostic and predictive value in cancer. Little is known regarding expression patterns of p27 in renal cell carcinoma (RCC) or how p27 participates in disease progression or response to therapy. EXPERIMENTAL
designRCC-derived cell lines, primary tumors, and normal renal epithelial cells were analyzed for p27 expression, phosphorylation (T157 of the NLS), and subcellular localization. RCC-derived cell lines were treated with phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitors and effects on p27 localization were assessed. The potential contribution of cytoplasmic p27 to resistance to apoptosis was also evaluated.
resultsp27 was elevated in tumors compared with matched controls, and cytoplasmic mislocalization of p27 was associated with increasing tumor grade. Cytoplasmic localization of p27 correlated with phosphorylation at T157, an AKT phosphorylation site in the p27 NLS. In RCC cell lines, activated PI3K/AKT signaling was accompanied by mislocalization of p27. AKT activation and phosphorylation of p27 was associated with resistance to apoptosis, and small interfering RNA knockdown of p27 or relocalization to the nucleus increased apoptosis in RCC cells. Treatment with the PI3K inhibitors LY294002 or wortmannin resulted in nuclear relocalization of p27, whereas mTOR inhibition by rapamycin did not.
conclusionsIn RCC, p27 is phosphorylated at T157 of the NLS, with increasing tumor grade associated with cytoplasmic p27. PI3K inhibition (which reduces AKT activity) reduces T157 phosphorylation and induces nuclear relocalization of p27, whereas mTOR inhibition does not. Clinical testing of these findings may provide a rational approach for use of mTOR and PI3K/AKT pathway inhibitors in patients with RCC.
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