IGF-1 increases invasive potential of MCF 7 breast cancer cells and induces activation of latent TGF-β1 resulting in epithelial to mesenchymal transition

Cell Communication and Signaling

Research

Sashko Damjanovski¹  Logan A Walsh¹ 

[1] Department of Biology, University of Western Ontario, N6A 5B7, Ontario, London, Canada;

关键词: PI3K Inhibitor;    Metalloproteinase Activity;    Marker Gene Expression;    Hs578t Cell;    Fluorogenic Peptide Substrate;   

DOI  :  10.1186/1478-811X-9-10

 received in 2010-11-03, accepted in 2011-05-02,  发布年份 2011

来源: Springer

【 摘 要 】

IntroductionTGF-β signaling has been extensively studied in many developmental contexts, amongst which is its ability to induce epithelial to mesenchymal transitions (EMT). EMTs play crucial roles during embryonic development and have also come under intense scrutiny as a mechanism through which breast cancers progress to become metastatic. Interestingly, while the molecular hallmarks of EMT progression (loss of cell adhesion, nuclear localization of β-catenin) are straightforward, the cellular signaling cascades that result in an EMT are numerous and diverse. Furthermore, most studies describing the biological effects of TGF-β have been performed using high concentrations of active, soluble TGF-β, despite the fact that TGF-β is produced and secreted as a latent complex.MethodsMCF-7 breast cancer cells treated with recombinant IGF-1 were assayed for metalloproteinase activity and invasiveness through a matrigel coated transwell invasion chamber. IGF-1 treatments were then followed by the addition of latent-TGF-β1 to determine if elevated levels of IGF-1 together with latent-TGF-β1 could cause EMT.ResultsResults showed that IGF-1 - a molecule known to be elevated in breast cancer is a regulator of matrix metalloproteinase activity (MMP) and the invasive potential of MCF-7 breast cancer cells. The effects of IGF-1 appear to be mediated through signals transduced via the PI3K and MAPK pathways. In addition, increased IGF-1, together with latent TGF-β1 and active MMPs result in EMT.ConclusionsTaken together our data suggest a novel a link between IGF-1 levels, MMP activity, TGF-β signaling, and EMT in breast cancer cells.

【 授权许可】

CC BY   
© Walsh and Damjanovski; licensee BioMed Central Ltd. 2011