ArticleOncotarget2014
Mislocalization of p27 to the cytoplasm of breast cancer cells confers resistance to anti-HER2 targeted therapy.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- p27 Expression in Wild-Type KRAS Colon Cancer.Journal of cellular and molecular medicine · 2026Article
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- Suppressive cancer nonstop extension mutations increase C-terminal hydrophobicity and disrupt evolutionarily conserved amino acid patterns.Nature communications · 2024Article
- Construction and validation of a prognostic risk model for breast cancer based on protein expression.BMC medical genomics · 2022Article
- Regulation of p27 (Kip1) by Ubiquitin E3 Ligase RNF6.Pharmaceutics · 2022Article
- FMNL2 suppresses cell migration and invasion of breast cancer: a reduction of cytoplasmic p27 via RhoA/LIMK/Cofilin pathway.Cell death discovery · 2022Article
- The PTEN and ATM axis controls the G1/S cell cycle checkpoint and tumorigenesis in HER2-positive breast cancer.Cell death and differentiation · 2021Article
- Intrinsically Disordered Proteins as Regulators of Transient Biological Processes and as Untapped Drug Targets.Molecules (Basel, Switzerland) · 2021Review
- CDKN1B mutation and copy number variation are associated with tumor aggressiveness in luminal breast cancer.The Journal of pathology · 2021Article
- Targeting intrinsically disordered proteins involved in cancer.Cellular and molecular life sciences : CMLS · 2020Review
- Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma.Journal of cell communication and signaling · 2019Article
- The Multifaceted p21 (Cip1/Waf1/Cancers · 2019Review
- Correlation of constitutive photomorphogenic 1 (COP1) and p27 tumor suppressor protein expression in ovarian cancer.Genes & genomics · 2019Article
- CACYBP Enhances Cytoplasmic Retention of P27Theranostics · 2019Article
- Suppression of AURKA alleviates p27 inhibition on Bax cleavage and induces more intensive apoptosis in gastric cancer.Cell death & disease · 2018Article
- A Small Molecule Causes a Population Shift in the Conformational Landscape of an Intrinsically Disordered Protein.Journal of the American Chemical Society · 2017Article
- Epidermal Growth Factor Receptor activation promotes ADA3 acetylation through the AKT-p300 pathway.Cell cycle (Georgetown, Tex.) · 2017Article
- Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance.Oncotarget · 2016Article
- Discovery of Small Molecules that Inhibit the Disordered Protein, p27(Kip1).Scientific reports · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
As a cell cycle inhibitor and tumor suppressor, p27 is frequently misregulated in human cancers. Increased degradation is the most common mechanism of misregulation, however in some cancers, p27 is mislocalized from its cell cycle inhibitory location in the nucleus, to the cytoplasm. In normal cells cytoplasmic p27 has functions that are distinct from its cell cycle-regulatory nuclear functions. Therefore, an important question is whether localization of p27 to the cytoplasm in tumor cells is primarily a mechanism for cancelling its inhibitory effect on cell proliferation, or whether cytoplasmic p27 has more direct oncogenic actions. To study p27 mislocalization in human cancers we screened a panel of common breast cancer cell lines. We observed that p27 accumulated in the cytoplasm exclusively in cell lines that are Her2+. To address the significance of p27 mislocalization in Her2+ breast cancer cells we interrogated the cellular response to the dual-Her2/EGFR kinase inhibitor, lapatinib. Knockdown of p27 using shRNA sensitized Her2+ cells to lapatinib-induced apoptosis. Moreover, expression of a constitutively cytoplasmic form of p27 (p27ΔNLS) reversed the lapatinib-induced apoptosis, suggesting that cytoplasmic p27 contributed to lapatinib resistance in Her2+ breast cancer cells by suppressing apoptosis. Our results suggest that p27 localization may be useful as a predictive biomarker of therapeutic response in patients with Her2+ breast cancers.
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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.