ArticleFrontiers in endocrinology2019
Insulin Enhances Migration and Invasion in Prostate Cancer Cells by Up-Regulation of FOXC2.
Article in Frontiers in endocrinology, 2019. 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, 27 citations in OpenAlex.
- Assessing the Feasibility of a Self-Management Intervention for Individuals With Advanced Prostate Cancer and Comorbid Type II Diabetes Mellitus.Cancer medicine · 2026Trial
- Non-Fasting Glucose Measures and Their Clinical Significance in Diabetes Diagnosis and Cardiovascular and Cancer Risk Prediction: A Narrative Review.International journal of molecular sciences · 2026Review
- Article
- Modulation of the Epithelial-mesenchymal transition process by Forkhead Box C2 in the repair of airway epithelium after injury.Respiratory research · 2025Article
- The effects of glycemic index on prostate cancer progression in a xenograft mouse model.Prostate cancer and prostatic diseases · 2024Article
- Body mass index, triglyceride-glucose index, and prostate cancer death: a mediation analysis in eight European cohorts.British journal of cancer · 2024Article
- In Vitro Simulated Ketogenic Diet Inhibits the Proliferation and Migration of Liver Cancer Cells by Reducing Insulin Production and Down-regulating FOXC2 Expression.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- Effects of T2DM on cancer progression: pivotal precipitating factors and underlying mechanisms.Frontiers in endocrinology · 2024Review
- The Insulin Receptor Substrate 2 Mediates the Action of Insulin on HeLa Cell Migration via the PI3K/Akt Signaling Pathway.Current issues in molecular biology · 2023Article
- Dual STAT‑3 and IL‑6R inhibition with stattic and tocilizumab decreases migration, invasion and proliferation of prostate cancer cells by targeting the IL‑6/IL‑6R/STAT‑3 axis.Oncology reports · 2022Article
- C-Peptide Promotes Cell Migration by Controlling Matrix Metallopeptidase-9 Activity Through Direct Regulation of β-Catenin in Human Endometrial Stromal Cells.Frontiers in cell and developmental biology · 2022Article
- Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective.Oncology research · 2022Review
- Identifying the Antitumor Effects of Curcumin on Lung Adenocarcinoma Using Comprehensive Bioinformatics Analysis.Drug design, development and therapy · 2022Article
- Super-enhancer Acquisition Drives FOXC2 Expression in Middle Ear Cholesteatoma.Journal of the Association for Research in Otolaryngology : JARO · 2021Article
- The Influence of Anti-Diabetic Drugs on Prostate Cancer.Cancers · 2021Review
- A constriction channel analysis of astrocytoma stiffness and disease progression.Biomicrofluidics · 2021Article
- Pharmacoepidemiological Evaluation in Prostate Cancer-Common Pitfalls and How to Avoid Them.Cancers · 2021Review
- Nonspectroscopic Migratory Cell Monitoring Method Using Retroreflective Janus Microparticles.ACS omega · 2020Article
- Transcript Levels of Aldo-Keto Reductase Family 1 Subfamily C (AKR1C) Are Increased in Prostate Tissue of Patients with Type 2 Diabetes.Journal of personalized medicine · 2020Article
- Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer (PCa), yet many patients relapse with lethal metastatic disease. With this loss of androgens, increased cell plasticity has been observed as an adaptive response to ADT. This includes gain of invasive and migratory capabilities, which may contribute to PCa metastasis. Hyperinsulinemia, which develops as a side-effect of ADT, has been associated with increased tumor aggressiveness and faster treatment failure. We investigated the direct effects of insulin in PCa cells that may contribute to this progression. We measured cell migration and invasion induced by insulin using wound healing and transwell assays in a range of PCa cell lines of variable androgen dependency (LNCaP, 22RV1, DuCaP, and DU145 cell lines). To determine the molecular events driving insulin-induced invasion we used transcriptomics, quantitative real time-PCR, and immunoblotting in three PCa cell lines. Insulin increased invasiveness of PCa cells, upregulating Forkhead Box Protein C2 (FOXC2), and activating key PCa cell plasticity mechanisms including gene changes consistent with epithelial-to-mesenchymal transition (EMT) and a neuroendocrine phenotype. Additionally, analysis of publicly available clinical PCa tumor data showed metastatic prostate tumors demonstrate a positive correlation between insulin receptor expression and the EMT transcription factor FOXC2. The insulin receptor is not suitable to target clinically however, our data shows that actions of insulin in PCa cells may be suppressed by inhibiting downstream signaling molecules, PI3K and ERK1/2. This study identifies for the first time, a mechanism for insulin-driven cancer cell motility and supports the concept that targeting insulin signaling at the level of the PCa tumor may extend the therapeutic efficacy of ADT.
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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 Socratic graph.