Snail promotes prostate cancer migration by facilitating SPOP ubiquitination and degradation.
Snail promotes prostate cancer migration by facilitating SPOP ubiquitination and degradation. Biochem Biophys Res Commun. 2020 Aug 27;529(3):799-804 Authors: Lv W, Huan M, Yang W, Gao Y, Wang K, Xu S, Zhang M, Ma J, Wang X, Chen Y, Li L Abstract Prostate cancer (PCa) is the second leading cause of cancer-associated mortality in men. Speckle-type pox virus and zinc finger protein (SPOP), the most frequently mutated gene in PCa, functions as a tumor suppressor via degradation of cancer-promoting substrates. However, its upstream regulation in PCa metastasis remains poorly determined. Here, in a Snail-induced metastatic PCa model, we observed an accelerated degradation of SPOP protein in cells, which is crucial for the PCa migration and activation of the AKT signaling pathway. Mechanistically, we demonstrated that binding to Snail promoted SPOP ubiquitination and degradation. Moreover, the bric-a-brac/tramtrack/broad complex (BTB) domain of SPOP is turned out to be essential for Snail-mediated SPOP degradation. Thus, our findings reveal a post-translational level regulation of SPOP expression that facilitates the metastasis of PCa cells. PMID: 32736710 [PubMed - as supplied by publisher]
British Journal of Cancer, Published online: 23 September 2020; doi:10.1038/s41416-020-01081-3Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank
British Journal of Cancer, Published online: 23 September 2020; doi:10.1038/s41416-020-01086-yBCAS2, a protein enriched in advanced prostate cancer, interacts with NBS1 to enhance DNA double-strand break repair
First, and perhaps most importantly, Dinh et al are to be applauded for presenting their prospective series of men treated with proton therapy at the University of Washington and their carefully reported rectal toxicity outcomes in the context of dose-volume histogram analysis as well as differing rectal immobilization devices.1 These result s provide strong evidence suggesting that without the use of a rectal spacer, there is increased rectal toxicity with proton therapy compared with intensity modulated radiation therapy (IMRT).
The recent meta-analysis of the dose-response rate of prostate cancer biochemical control during hypofractionated radiation therapy by Vogelius and Bentzen1 showed that the standard linear-quadratic model was insufficient to model the observed clinical response. They proposed 2 possible corrections: either (1) the slope of the α/β ratio increases by 0.6 for every Gray of increase in the dose per fraction or (2) there is an arbitrary limit to the dose-response curve at 80 Gy.
We thank Drs. Alfonso and Berk for their interest1 in our meta-analysis of outcome data from randomized controlled trials of hypofractionated radiation therapy for low-risk prostate cancer.2 Specifically, we showed how the recently published study of ultrahypofractionated radiation therapy by Widmark et al3 provides further evidence for a diminishing benefit from radiation therapy intensified by increasing the dose per fraction.2 This is a purely empirical observation and does not rely on any mechanistic assumptions.
Condition: Prostate Cancer Interventions: Drug: Testosterone Cypionate; Drug: Darolutamide Sponsors: Latin American Cooperative Oncology Group; Bayer Not yet recruiting
(University of Texas at Austin) Scientists have identified a driver of drug resistance in breast, ovarian and prostate cancers that may help doctors predict which patients will become resistant to a class of drugs frequently used to treat BRCA 1/2-deficient tumors.