ArticleEMBO molecular medicine2014
Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 103 citations in OpenAlex.
- Article
- MEOX1 Inhibits Growth and Metastasis of Salivary Adenoid Cystic Carcinoma.Current issues in molecular biology · 2026Article
- Clinicogenomic Landscape and Function ofJCO precision oncology · 2026Article
- Navigating chemoresistance in triple-negative breast cancer: interplay between molecular signalling pathways and immune microenvironment.Molecular biology reports · 2026Review
- Nrf3: an emerging player in cancer, inflammation, and cellular homeostasis.Molecular biology reports · 2026Review
- eEF2K is a poor prognostic factor and novel molecular target in pancreatic cancer: regulating tumor growth and progression via the tumor microenvironment.Cell death & disease · 2025Article
- Identification of a Novel Substrate for eEF2K and the AURKA-SOX8 as the Related Pathway in TNBC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- eEF2K as an important kinase associated with cancer survival and prognosis.Scientific reports · 2024Article
- PTEN deficiency induces an extrahepatic cholangitis-cholangiocarcinoma continuum via aurora kinase A in mice.Journal of hepatology · 2024Article
- Article
- DNA methylation profiling deciphers three EMT subtypes with distinct prognoses and therapeutic vulnerabilities in breast cancer.Journal of Cancer · 2024Article
- Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer.Nature communications · 2023Article
- Loss of Epigenetic Regulation Disrupts Lineage Integrity, Induces Aberrant Alveogenesis, and Promotes Breast Cancer.Cancer discovery · 2022Article
- Eukaryotic Extension Factor 2 Kinase may Affect the Occurrence and Development of Glioblastoma Through Immune Cell Infiltration.Neurochemical research · 2022Article
- Article
- The AKT1E17K Allele Promotes Breast Cancer in Mice.Cancers · 2022Article
- eEF2K promotes PD-L1 stabilization through inactivating GSK3β in melanoma.Journal for immunotherapy of cancer · 2022Article
- Common Genomic Aberrations in Mouse and Human Breast Cancers with Concurrent P53 Deficiency and Activated PTEN-PI3K-AKT Pathway.International journal of biological sciences · 2022Article
- Review
- YY1-mediated long non-coding RNA Kcnq1ot1 promotes the tumor progression by regulating PTEN via DNMT1 in triple negative breast cancer.Cancer gene therapy · 2021Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The tumor suppressors Pten and p53 are frequently lost in breast cancer, yet the consequences of their combined inactivation are poorly understood. Here, we show that mammary-specific deletion of Pten via WAP-Cre, which targets alveolar progenitors, induced tumors with shortened latency compared to those induced by MMTV-Cre, which targets basal/luminal progenitors. Combined Pten-p53 mutations accelerated formation of claudin-low, triple-negative-like breast cancer (TNBC) that exhibited hyper-activated AKT signaling and more mesenchymal features relative to Pten or p53 single-mutant tumors. Twenty-four genes that were significantly and differentially expressed between WAP-Cre:Pten/p53 and MMTV-Cre:Pten/p53 tumors predicted poor survival for claudin-low patients. Kinome screens identified eukaryotic elongation factor-2 kinase (eEF2K) inhibitors as more potent than PI3K/AKT/mTOR inhibitors on both mouse and human Pten/p53-deficient TNBC cells. Sensitivity to eEF2K inhibition correlated with AKT pathway activity. eEF2K monotherapy suppressed growth of Pten/p53-deficient TNBC xenografts in vivo and cooperated with doxorubicin to efficiently kill tumor cells in vitro. Our results identify a prognostic signature for claudin-low patients and provide a rationale for using eEF2K inhibitors for treatment of TNBC with elevated AKT signaling.
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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.