Activins and Inhibins in Endocrine and Other Tumors

Abstract

Inhibin and activin are members of the TGF beta superfamily of growth and differentiation factors. They were first identified as gonadal-derived regulators of pituitary FSH and were subsequently assigned multiple actions in a wide range of tissues. More recently, the inhibin alpha subunit was considered as a tumor suppressor based on functional studies employing transgenic mouse models. This review evaluates the functional and molecular evidence that the inhibin alpha subunit is a tumor suppressor in endocrine cancers. The evaluation highlights the discrepant results from the human and mouse studies, as well as the differences between endocrine tumor types. In addition, we examine the evidence that the activin-signaling pathway is tumor suppressive and identify organ-specific differences in the actions and putative roles of this pathway in endocrine tumors. In summary, there is a considerable body of evidence to support the role of inhibins and activins in endocrine-related tumors. Future studies will define the mechanisms by which inhibins and activins contribute to the process of initiation, promotion, or progression of endocrine-related cancers.

Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer

“…However, the functional role of AKTIP could be tumor type-specific, since it has been proposed as a putative oncoprotein in cervical cancer but a tumor suppressor in ovarian cancer (Cinghu et al 2011;Notaridou et al 2011). INHBA encodes inhibin beta A, a subunit of both the activin and inhibin receptors of the transforming growth factor (TGF-beta) superfamily (Risbridger et al 2001). Inhibin beta A, like TGF-beta, can inhibit or stimulate cell growth dependent on the cellular context.…”

The bright and the dark sides of activin in wound healing and cancer

“…Accordingly, to allow malignant progression, these cancer cells and tissues acquire resistance to activin by downregulating the expression of activin receptors. Tissues whose growth is promoted by activin include the testis and ovary; here, activin acts as a mitogen for the tumour cells (reviewed by Risbridger et al, 2001). In addition to a direct effect on tumour cells, several studies indicate that activin can also affect tumorigenesis by altering the tumour microenvironment.…”

Activin A Suppresses Osteoblast Mineralization Capacity by Altering Extracellular Matrix (ECM) Composition and Impairing Matrix Vesicle (MV) Production

“…Inhibins exert their inhibitory effects on activin by competitive binding to the activin receptors in the presence of betaglycan. This signaling regulates a wide array of biological activities from cell proliferation, differentiation to tumor development and endocrine signaling (5,6) in many cell lineages like hematopoietic (7,8) and monocyte/macrophage (9,10). Several consequences of these reproductive hormones, especially those of activin A, are also described in relation to bone metabolism.…”