A) Human epidermoid carcinoma A431 cells, untreated (top) or treated (bottom) with 5 M TSA (16 h). Acetylated cytoplasmic and nuclear proteins were visualized in green fluorescence.  B) Silver stain of acetyl-lysine immunoprecipitates from wild-type (WT) and muscle-specific knock-out of E1a-binding protein (mKO) mice.
Figure 1: Rac1 is activated in serum treated migrating Swiss 3T3 fibroblasts, as shown by staining for F-actin rich lamellipodia with rhodamine phalloidin (Cat. # PHDR1).

Recently, Qin et al. studied the interplay between matrix metalloproteinase-8 (MMP-8) and transforming growth factor beta 1 (TGF-b1) and the effect on each protein’s expression and activity levels in hepatocellular carcinoma (HCC) cells as HCC is responsible for most primary liver cancers.  MMPs are integral for tumor cell metastasis and invasion while TGF-b1 drives cancer progression via epithelial-mesenchymal transition (EMT) and induction of MPP expression.  The authors found that the proteins reciprocally activate each other, leading to increased EMTs and HCC metastasis and invasion in vitro. Moreover, each protein rescues the depleted expression of the other in vitro. In both cases, the PI3K/Akt/Rac1 signaling pathway is the primary mediator as demonstrated pharmacologically. Furthermore, overexpression of MMP-8 or TGF-b1 increases PI3K/Akt/Rac1 pathway activity whereas knockdown exerts the opposite effect.  Cytoskeleton’s Rac1 G-LISA activation assay kit (Cat.# BK128) was an essential reagent in this study as it provided consistent, sensitive, and quantitative measurement of Rac1 activity following manipulation of the expression and activity levels of MMP-8 and TGF-b1. Thus, Rac1 activation mediates the downstream effects of MMP-8/TGF-b1 interplay that results in increased EMT and HCC metastasis and invasion.

Link to citation: 

Qin G. et al. 2016. Reciprocal activation between MMP-8 and TGF-b1 stimulates EMT and malignant progression of hepatocellular carcinoma. Cancer Lett. 374, 85-95.

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alex castellanos