Abstract
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.
Highlights
TGF-b signaling has been extensively studied in many developmental contexts, amongst which is its ability to induce epithelial to mesenchymal transitions (EMT)
Results showed that insulin-like growth factor (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
Increased IGF-1, together with latent TGF-b1 and active MMPs result in EMT
Summary
TGF-b signaling has been extensively studied in many developmental contexts, amongst which is its ability to induce epithelial to mesenchymal transitions (EMT). Most cancers, usurp cellular signaling pathways, developmental pathways, that are normally tightly regulated in the animal or embryo Alteration of these pathways often results in oncogenic transformations. Between IGF-1 levels and breast cancer, especially among premenopausal women [4] Another potent signaling molecule that is correlated with changes in cellular morphology and migration is TGF-b. While many studies have investigated TGF-b’s role in regulating EMTs, most studies describing biological effects of TGF-b have been carried out in vitro using high concentrations of active, soluble TGF-b, despite the fact that TGF-b is produced and secreted in vivo as a latent complex [9]. While much is known about TGF-b signaling in comparison, the mechanism of TGF-b activation, and its relationship to IGF-1 in breast cancer metastasis, is poorly understood
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