ArticleMolecular cancer2023
STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.
Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- Circadian synchronization between diet and gut microbiota in modulating host's health.Gut microbes · 2026Review
- Metformin in prostate cancer: a context-dependent antitumour strategy driven by metabolic vulnerability and signalling network.Discover oncology · 2026Review
- Biobank of genetically defined murine prostate cancer tumoroids uncovers oncogenic pathways and drug vulnerabilities driven by PTEN-loss.Cell reports methods · 2026Article
- A Deep Learning-Based Multimodal Clinico-Histology-Genomic Prognostic Model in Prostate Cancer.Annals of surgical oncology · 2026Article
- STAT1/3/5 Functions Driving Lipid and Energy Metabolism in Cancer and Immunity.International journal of molecular sciences · 2026Review
- lnc-ALX1-2:10 is a novel regulator that enhances proliferation, migration and invasion in prostate cancer cells.Scientific reports · 2026Article
- Notch-1 suppressed vascular dementia via modulating AMPK/mTOR/TFEB/YAP signaling induced ferroptosis.European journal of medical research · 2026Article
- EGFR-STAT3 activation provides a therapeutic rationale for targeting aggressive ETV1-positive prostate cancer.Molecular oncology · 2025Article
- Loss of STAT3 in acute myeloid leukemia favors tissue infiltration linked to CXCR4 signaling.Blood neoplasia · 2025Article
- Deletion of ZNRF2 Exacerbates MPTP-Induced Parkinson's Disease by Activating mTOR-Mediated Neuroinflammatory Pathways.Molecular neurobiology · 2025Article
- Hsa_circ_0026782 Acts as a "Molecular Break" of CREB1-Mediated Transcription by Promoting Its Phosphorylation at Ser142 That Prevents Keloid Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metformin and Adipose Tissue: A Multifaceted Regulator in Metabolism, Inflammation, and Regeneration.Endocrinology and metabolism (Seoul, Korea) · 2025Review
- The anti-diabetic PPARγ agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer.Molecular cancer · 2025Article
- The LysoPS/GPR174 axis drives metastatic progression in esophageal squamous cell carcinoma through cAMP-PKA-CREB signaling activation.Journal of translational medicine · 2025Article
- Goistrat: gene-of-interest-based sample stratification for the evaluation of functional differences.BMC bioinformatics · 2025Article
- Cellular and Molecular Evidence of the Synergistic Antitumour Effects of Hydroxytyrosol and Metformin in Prostate Cancer.International journal of molecular sciences · 2025Article
- The Impact of Diabetes and Antidiabetics on Uro-Oncological Disease Outcomes: A Single-Center Experience.Urologia internationalis · 2025Article
- Androgen receptor dynamics in prostate cancer: from disease progression to treatment resistance.Frontiers in oncology · 2025Review
- Unleashing the power of peptides in prostate cancer immunotherapy: mechanism, facts and perspectives.Frontiers in pharmacology · 2025Review
- Androgen Signaling in Prostate Cancer: When a Friend Turns Foe.Endocrine, metabolic & immune disorders drug targets · 2025Review
Corrections and comments
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Authors and funding
55 authors at 20 institutions in 10 countries.
Funding
Abstract
Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa. Here we show a frequent genomic co-deletion of PTEN and STAT3 in liquid biopsies of patients with mPCa. Loss of Stat3 in a Pten-null mouse prostate model leads to a reduction of LKB1/pAMPK with simultaneous activation of mTOR/CREB, resulting in metastatic disease. However, constitutive activation of Stat3 led to high LKB1/pAMPK levels and suppressed mTORC1/CREB pathway, preventing mPCa development. Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis. We find that metformin treatment of STAT3/AR-expressing PCa xenografts resulted in significantly reduced tumor growth accompanied by diminished mTORC1/CREB, AR and PSA levels. PCa xenografts with deletion of STAT3/AR nearly completely abrogated mTORC1/CREB inhibition mediated by metformin. Moreover, metformin treatment of PCa patients with high Gleason grade and type 2 diabetes resulted in undetectable mTORC1 levels and upregulated STAT3 expression. Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa.
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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.