文章基本信息

标题：Solid stress-induced migration is mediated by GDF15 through Akt pathway activation in pancreatic cancer cells
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作者：Maria Kalli ; Angeliki Minia ; Vaia Pliaka 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-12
DOI：10.1038/s41598-018-37425-6
出版社：Springer Nature
摘要：Solid stress is a biomechanical abnormality of the tumor microenvironment that plays a crucial role in tumor progression. When it is applied to cancer cells, solid stress hinders their proliferation rate and promotes cancer cell invasion and metastatic potential. However, the underlying mechanisms of how it is implicated in cancer metastasis is not yet fully understood. Here, we used two pancreatic cancer cell lines and an established in vitro system to study the effect of solid stress-induced signal transduction on pancreatic cancer cell migration as well as the mechanism involved. Our results show that the migratory ability of cells increases as a direct response to solid stress. We also found that Growth Differentiation Factor 15 (GDF15) expression and secretion is strongly upregulated in pancreatic cancer cells in response to mechanical compression. Performing a phosphoprotein screening, we identified that solid stress activates the Akt/CREB1 pathway to transcriptionally regulate GDF15 expression, which eventually promotes pancreatic cancer cell migration. Our results suggest a novel solid stress signal transduction mechanism bringing GDF15 to the centre of pancreatic tumor biology and rendering it a potential target for future anti-metastatic therapeutic innovations.