ArticleCancer discovery2015
MYC Drives Pten/Trp53-Deficient Proliferation and Metastasis due to IL6 Secretion and AKT Suppression via PHLPP2.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 77 citations in OpenAlex.
- Evaluation of triplet therapy combined with robot-assisted cytoreductive prostatectomy for high-volume metastatic prostate cancer: a multicentre randomised controlled trial protocol.BJU international · 2026Article
- Nuclear adenosine metabolism defines a metabolic vulnerability unmasked by TP53 loss.bioRxiv : the preprint server for biology · 2026Article
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Inhibiting stearoyl-CoA desaturase suppresses bone metastatic prostate cancer by modulating cellular stress, mTOR signaling, and DNA damage response.FEBS letters · 2026Article
- OGT-Mediated O-GlcNAcylation Stabilizes c-Myc Activity and Promotes Chemoresistance in Triple-Negative Breast Cancer.The breast journal · 2026Article
- CD24 and Mutant p53: Emerging Therapeutic Targets in Prostate Cancer Progression.Anti-cancer agents in medicinal chemistry · 2026Review
- Cooperative role of distinctive TP53 and PTEN combined loss in the peripheral T cell lymphoma-GATA3 molecular subgroup.Science advances · 2025Article
- Tumor Immune Microenvironment and Checkpoint Inhibition in Clear Cell Ovarian Carcinoma: Bridging Tumor Biology and Clinical Application in Immunotherapy.Current issues in molecular biology · 2025Review
- Polydatin: A natural compound with multifaceted anticancer properties.Journal of traditional and complementary medicine · 2025Review
- Engineered EVs-Mediated miR-222 Targeting PTEN/FN1 Axis Reverses Anthracycline Resistance in HER2-Negative Breast Cancer.Cancer science · 2025Article
- p53-loss induced prostatic epithelial cell plasticity and invasion is driven by a crosstalk with the tumor microenvironment.Cell death & disease · 2025Article
- Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function.Science (New York, N.Y.) · 2024Article
- Clonal Lineage Tracing with Somatic Delivery of Recordable Barcodes Reveals Migration Histories of Metastatic Prostate Cancer.Cancer discovery · 2024Article
- Mutant TP53 switches therapeutic vulnerability during gastric cancer progression within interleukin-6 family cytokines.Cell reports · 2024Article
- Regulation of Molecular Biomarkers Associated with the Progression of Prostate Cancer.International journal of molecular sciences · 2024Review
- FABP5 Inhibition againstCancers · 2023Article
- Regulation of EZH2 Expression by INPP4B in Normal Prostate and Primary Prostate Cancer.Cancers · 2023Article
- Pten knockout affects drug resistance differently in melanoma and kidney cancer.Pharmacological reports : PR · 2023Article
- Pre-Clinical Models to Study Human Prostate Cancer.Cancers · 2023Review
- Molecular and metabolic regulation of immunosuppression in metastatic pancreatic ductal adenocarcinoma.Molecular cancer · 2023Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledWe have recently recapitulated metastasis of human PTEN/TP53-mutant prostate cancer in the mouse using the RapidCaP system. Surprisingly, we found that this metastasis is driven by MYC, and not AKT, activation. Here, we show that cell-cell communication by IL6 drives the AKT-MYC switch through activation of the AKT-suppressing phosphatase PHLPP2, when PTEN and p53 are lost together, but not separately. IL6 then communicates a downstream program of STAT3-mediated MYC activation, which drives cell proliferation. Similarly, in tissues, peak proliferation in Pten/Trp53-mutant primary and metastatic prostate cancer does not correlate with activated AKT, but with STAT3/MYC activation instead. Mechanistically, MYC strongly activates the AKT phosphatase PHLPP2 in primary cells and prostate cancer metastasis. We show genetically that Phlpp2 is essential for dictating the proliferation of MYC-mediated AKT suppression. Collectively, our data reveal competition between two proto-oncogenes, MYC and AKT, which ensnarls the Phlpp2 gene to facilitate MYC-driven prostate cancer metastasis after loss of Pten and Trp53. SIGNIFICANCE: Our data identify IL6 detection as a potential causal biomarker for MYC-driven metastasis after loss of PTEN and p53. Second, our finding that MYC then must supersede AKT to drive cell proliferation points to MYC inhibition as a critical part of PI3K pathway therapy in lethal prostate cancer.
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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.