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Review
. 2023 Feb 1;324(2):C428-C437.
doi: 10.1152/ajpcell.00178.2022. Epub 2023 Jan 9.

Evolving roles of activins and inhibins in ovarian cancer pathophysiology

Elizabeth T Evans  1 , Ben Horst  2 , Rebecca C Arend  1 , Karthikeyan Mythreye  2
Affiliations
Review

Evolving roles of activins and inhibins in ovarian cancer pathophysiology

Elizabeth T Evans et al. Am J Physiol Cell Physiol. .

Abstract

Activins and inhibins are unique members of the transforming growth factor-β (TGFβ) family of growth factors, with the ability to exert autocrine, endocrine, and paracrine effects in a wide range of complex physiologic and pathologic processes. Although first isolated within the pituitary, emerging evidence suggests broader influence beyond reproductive development and function. Known roles of activin and inhibin in angiogenesis and immunity along with correlations between gene expression and cancer prognosis suggest potential roles in tumorigenesis. Here, we present a review of the current understanding of the biological role of activins and inhibins as it relates to ovarian cancers, summarizing the underlying signaling mechanisms and physiologic influence, followed by detailing their roles in cancer progression, diagnosis, and treatment.

Keywords: TGFβ superfamily; activin; inhibin; ovarian cancer; tumor immune environment.

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Conflict of interest statement

Dr. Karthikeyan Mythreye served as Guest Editor of the special collection in which this article appears but was not involved and did not have access to information regarding the peer-review process or final disposition of this article.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Activin and inhibin signaling. A: dimeric activin, composed of two β-subunits, binds first to cell surface type II activin receptors (ActIIA or ActIIB) with resulting recruitment of the type I receptors (ALK4 and ALK7). The formation of this complex elicits cellular responses by the activation of a phosphorylation cascade, first of SMAD2/3 followed by co-complex formation with SMAD4. The SMAD complex is then able to translocate into the nucleus where it exerts its affect via changes in gene transcription. B: i) heterodimeric inhibin in epithelial cells interacts with co-receptor betaglycan via the α subunit which allows ternary complex formation with the type II ActRIIA/B receptors, resulting in exclusion of the type I receptors and no resulting SMAD phosphorylation. ii) In endothelial cells, dimeric inhibin A promotes complex formation between the co-receptor endoglin and the endothelial type I receptor ALK1 that can potentially phosphorylate SMAD1/5. Figure created with BioRender.com.
See this image and copyright information in PMC

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