41 research outputs found
Esophageal squamous cell carcinoma invasion is inhibited by Activin A in ACVRIB-positive cells
Two-Edged Sword: How Activation Of The “Proto-Oncogene” Yes-Associated Protein 1 In Lung Squamous Cell Carcinoma Can Surprisingly Inhibit Tumor Growth
Putting the Pieces Together: NOD-Like Receptor Protein 3 Inflammasome Priming and Activation in Barrett's Epithelial Cells
Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion
In recent years, a significant amount of research has examined the controversial role of activin A in cancer. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, is best characterized for its function during embryogenesis in mesoderm cell fate differentiation and reproduction. During embryogenesis, TGFβ superfamily ligands, TGFβ, bone morphogenic proteins (BMPs) and activins, act as potent morphogens. Similar to TGFβs and BMPs, activin A is a protein that is highly systemically expressed during early embryogenesis; however, post-natal expression is overall reduced and remains under strict spatiotemporal regulation. Of importance, normal post-natal expression of activin A has been implicated in the migration and invasive properties of various immune cell types, as well as endometrial cells. Aberrant activin A signaling during development results in significant morphological defects and premature mortality. Interestingly, activin A has been found to have both oncogenic and tumor suppressor roles in cancer. Investigations into the role of activin A in prostate and breast cancer has demonstrated tumor suppressive effects, while in lung and head and neck squamous cell carcinoma, it has been consistently shown that activin A expression is correlated with increased proliferation, invasion and poor patient prognosis. Activin A signaling is highly context-dependent, which is demonstrated in studies of epithelial cell tumors and the microenvironment. This review discusses normal activin A signaling in comparison to TGFb and highlights how its dysregulation contributes to cancer progression and cell invasion
Su1913 Activin a Stifles Esophageal Squamous Cell Invasion in a Premalignant but Not Malignant Microenvironment
Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner1
Esophageal cancer, which frequently exhibits coordinated loss of E-cadherin (Ecad) and transforming growth factor β (TGFβ) receptor II (TβRII), has a high mortality rate. In a three-dimensional organotypic culture model system, esophageal keratinocytes expressing dominant-negative mutant versions of both Ecad and TβRII (ECdnT) invade into the underlying matrix embedded with fibroblasts. We also find that cathepsin B induction is necessary for fibroblast-mediated invasion. Furthermore, the ECdnT cells in this physiological context activate fibroblasts through the secretion of TGFβ1, which, in turn, is activated by cathepsin B. These results suggest that the interplay between the epithelial compartment and the surrounding microenvironment is crucial to invasion into the extracellular matrix