title: Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion.
abstract: 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.
authors.affiliation: Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. holli.a.loomans@vanderbilt.edu.
authors.forename: Holli A
authors.initials: HA
authors.lastname: Loomans
authors.affiliation: Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. claudia.andl@vanderbilt.edu.
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Andl