Abstract

Activin, a member of the TGF-β superfamily, is involved in many physiological processes, such as embryonic development and follicle development, as well as in multiple human diseases including cancer. Genetic mutations in the activin signaling pathway have been reported in many cancer types, indicating that activin signaling plays a critical role in tumorigenesis. Recent evidence reveals that activin signaling may function as a tumor-suppressor in tumor initiation, and a promoter in the later progression and metastasis of tumors. This article reviews many aspects of activin, including the signaling cascade of activin, activin-related proteins, and its role in tumorigenesis, particularly in pancreatic cancer development. The mechanisms regulating its dual roles in tumorigenesis remain to be elucidated. Further understanding of the activin signaling pathway may identify potential therapeutic targets for human cancers and other diseases.

Highlights

  • Activins are growth factors of the transforming growth factor-β (TGF-β) superfamily.The TGF-β superfamily proteins are involved in embryonic development and skin morphogenesis, and hold the key to the development of many human diseases, including cancers

  • This review focuses on the activin signaling pathway and its role in tumorigenesis, especially pancreatic cancer

  • A multitude of genomic studies have shown that activin/TGFβ is one of the core signaling pathways frequently disrupted in pancreatic ductal adenocarcinoma (PDAC)

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Summary

Introduction

Activins are growth factors of the transforming growth factor-β (TGF-β) superfamily. The TGF-β superfamily proteins are involved in embryonic development and skin morphogenesis, and hold the key to the development of many human diseases, including cancers. Activin shares similar structures with other members of the TGF-β superfamily proteins and has a parallel signaling pathway to transduce signals from the extracellular compartment into the nucleus. In comparison to the TGF-β and bone morphogenesis (BMPs) pathways in the TGF-β superfamily, activin signaling is less well understood. An aberrant activin signaling pathway has been found to be associated with several disease conditions, including preterm labor with delivery, osteoporosis, cancer, and cancer-related cachexia [2,3,4,5,6].

Components of the Activin Signaling Pathway
Regulation of the Activin Signaling Pathway
Embryogenesis and Hair Follicle Development
Tumor Suppression
Tumor Progression and Metastasis
Activin Signaling and the Development of the Pancreas
Dual Roles of Activin Signaling in Pancreatic Tumorigenesis
Conclusions
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