Tumor growth generates mechanical compression, which may trigger mechanotransduction in cancer and stromal cells and promote tumor progression. However, very little is known about how compression stimulates signal transduction and contributes to tumor progression. In the present study, we demonstrated that compression enhances a tumor progression phenotype using an in vitro compression model, and validated the results from the in vitro model with high- and low-compressed breast cancer tissues. Mechanical compression induced miR-9 downregulation by DNMT3A-dependent promoter methylation in the MDA-MB-231 and BT-474 breast cancer cell lines and in cancer-associated fibroblasts. The overexpression of miR-9 target genes (LAMC2, ITGA6, and EIF4E) was induced by miR-9 downregulation, which eventually enhanced vascular endothelial growth factors production. Demethylation and decompression could reverse compression-induced miR-9 downregulation and following overexpression of miR-9 target genes and VEGFA.

Tumor growth increases compressive stress within a tissue, which is associated with solid tumor progression. However, very little is known about how compressive stress contributes to tumor progression. Here, we show that compressive stress induces glycolysis in human breast cancer associated fibroblast (CAF) cells and thereby contributes to the expression of epithelial to mesenchymal (EMT)- and angiogenesis-related genes in breast cancer cells. Lactate production was increased in compressed CAF cells, in a manner dependent on the expression of metabolic genes ENO2 , HK2 , and PFKFB3 . Conditioned medium from compressed CAFs promoted the proliferation of breast cancer cells and the expression of EMT and/or angiogenesis-related genes. In patient tissues with high compressive stress, the expression of compression-induced metabolic genes was significantly and positively correlated with EMT and/or angiogenesis-related gene expression and metastasis size. These findings illustrate a mechanotransduction pathway involving stromal glycolysis that may be relevant also for other solid tumours.

BackgroundProstate cancer (PCa) is the second most frequently diagnosed cancer in male. In South Korea, PCa incidence has increased significantly, while its mortality rate has decreased steadily. To optimize the distribution of public medical resources, it is essential to analyze the contemporary epidemiology of PCa.MethodsNational population data from the National Health Insurance Statistical Yearbook and the annual report of national cancer registration and statistics in Korea were assessed. From the data, the incidence, prevalence, and mortality rates of PCa were calculated. The data were presented with reference to other types of cancers occurring in various countries from different continents.ResultsFrom 2007 to 2013, PCa incidence doubled (from 5,516 per year to 10,855 per year), while its prevalence in Korean men tripled (from 18,830 to 51,411) during the same period. The mortality rate increased slightly, from 4.2 in 2000 to 5.9 in 2007 and 6.0 in 2013 (per 100,000, age adjusted). PCa incidence increased significantly faster in men aged < 70 years than in the older age group.ConclusionPCa prevalence in South Korea has increased significantly, mainly due to the rise in its incidence. As the country is facing major changes, including westernization of dietary habits and rapid population aging, its prevalence would continue to increase in near future.