ArticleCell death & disease2020
Hotspot mutant p53-R273H inhibits KLF6 expression to promote cell migration and tumor metastasis.
Article in Cell death & disease, 2020. 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, 60 citations in OpenAlex.
- Mutant p53Molecular oncology · 2026Article
- Conserved signaling pathways and transcriptional regulators drive ovarian aging across species.Poultry science · 2026Article
- Inhalable Mucoadhesive Redox-Triggered Nanotherapeutics for p53-Mediated Lung Cancer Therapy and Metastasis Suppression.Advanced healthcare materials · 2026Article
- Transfer Learning for Survival-based Clustering of Predictors with an Application tobioRxiv : the preprint server for biology · 2025Article
- A base editing platform for the correction of cancer driver mutations unmasks conserved p53 transcription programs.Genome biology · 2025Article
- PDCD11 Stabilizes C-MYC Oncoprotein by Hindering C-MYC-SKP2 Negative Feedback Loop to Facilitate Progression of p53-Mutant Breast and Colon Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A pan-cancer analysis of the prognostic and immunological roles of zinc finger protein 514 in human tumors.Frontiers in oncology · 2025Article
- Promising Proteolysis-Targeting Chimera for Mutant p53-R175H.ACS omega · 2024Article
- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
- ECRG2/SPINK7 Tumor Suppressor as Modulator of DNA Damage Response.International journal of molecular sciences · 2024Review
- FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.PLoS biology · 2023Article
- Raf/MEK/ERK Signaling Pathway Is Involved in the Inhibition of Glioma Cell Proliferation and Invasion in the Ketogenic Microenvironment.Current medical science · 2023Article
- CCT8 promotes cell migration and tumor metastasis in lung adenocarcinomas.Journal of Cancer · 2023Article
- ER stress activates TAp73α to promote colon cancer cell apoptosis via the PERK-ATF4 pathway.Journal of Cancer · 2023Article
- Transition of amyloid/mutant p53 from tumor suppressor to an oncogene and therapeutic approaches to ameliorate metastasis and cancer stemness.Cancer cell international · 2022Review
- Complete Models of p53 Better Inform the Impact of Hotspot Mutations.International journal of molecular sciences · 2022Article
- Triptolide promotes degradation of the unfolded gain-of-function Tp53Translational lung cancer research · 2022Article
- Cross-talk between mutant p53 and p62/SQSTM1 augments cancer cell migration by promoting the degradation of cell adhesion proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Contribution of p53 in sensitivity to EGFR tyrosine kinase inhibitors in non-small cell lung cancer.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hotspot p53 mutant proteins often gain novel functions in promoting tumor metastases. However, the molecular mechanisms by which mutant p53 exerts gain-of-function in cancer are not totally understood. In this study, we demonstrate that hotspot mutant p53, p53-R273H, promotes cell scattering growth and migration via inhibiting the expression of Krupple-like factor 6 (KLF6), a Zinc finger transcription factor and a documented tumor suppressor. Restoration of KLF6 increases the expression of E-cadherin downregulated by p53-R273H and inhibits p53-R273H-induced cell migration and tumor metastasis. Further, p53-R273H reduces KLF6 transcription by upregulating EGFR expression which in turn activates AKT-FOXO1 axis. Pharmacological inhibitor of AKT, MK2206, rescues KLF6 expression and suppresses p53-R273H-induced cell migration. Clinical analyses reveal that KLF6 expression is decreased in human breast cancer specimens harboring p53 mutations, and negatively correlated with EGFR expression in human breast cancer. In addition, low expression of KLF6 is associated with poor overall survival (OS) and relapse-free survival (RFS) in p53 mutated human breast cancer patients. Together, these results reveal an important role for EGFR-AKT-FOXO1-KLF6-E-cadherin axis in mutant p53-induced cell migration and tumor metastasis.
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