New Australian (+Canadian) cell study below [1].
As we know, most PCa cells use fatty acids for energy - not glucose. This is why fluorodeoxyglucose (FDG) PET scans are not generally used. However, we also know that diabetics have less PCa risk than non-diabetics. This suggests that a die-off of pancreatic beta cells, which secrete insulin, may be protective.
(As an alternative to becoming diabetic, we can control insulin levels by avoiding glucose spikes. Metformin is helpful in that regard.)
In the new study:
"Insulin increased invasiveness of PCa cells, ... activating key PCa cell plasticity mechanisms including gene changes consistent with epithelial-to-mesenchymal transition (EMT) and a neuroendocrine phenotype." Nasty!
The context of the study, though, is ADT:
"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."
I must say that it is good to see some interest in insulin as something we need to target.
Note that the Triglycerides:HDL-Cholesterol ratio is a surrogate for insulin resistance. ("Resistance" means that we over-produce insulin in an attempt to overcome cellular resistance to it.)
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/313...
Front Endocrinol (Lausanne). 2019 Jul 17;10:481. doi: 10.3389/fendo.2019.00481. eCollection 2019.
Insulin Enhances Migration and Invasion in Prostate Cancer Cells by Up-Regulation of FOXC2.
Sarkar PL1, Lee W1, Williams ED1, Lubik AA2, Stylianou N1, Shokoohmand A1, Lehman ML1,2, Hollier BG1, Gunter JH1, Nelson CC1.
Author information
1
Queensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
2
Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
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.
KEYWORDS:
FOXC2; androgen deprivation; epithelial to mesenchymal transition (EMT); hyperinsulinemia; invasion; prostate cancer
PMID: 31379747 PMCID: PMC6652804 DOI: 10.3389/fendo.2019.00481
CRPC - causes and prevention of 
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