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The role of CCN4/WISP-1 in the cancerous phenotype

Authors Nivison MP, Meier KE

Received 31 March 2018

Accepted for publication 9 June 2018

Published 27 August 2018 Volume 2018:10 Pages 2893—2903

DOI https://doi.org/10.2147/CMAR.S133915

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Professor Nakshatri


Mary P Nivison, Kathryn E Meier

Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA

Abstract: CCN proteins are secreted into the extracellular environment where they interact with both components of the extracellular matrix and with cell surface receptors to regulate cellular function. Through these interactions, CCNs act as extracellular ligands to activate intracellular signal transduction pathways. CCN4/WISP-1, like other CCNs, plays multiple physiologic roles in development and also participates in pathogenesis. CCN4 is of particular interest with respect to cancer, showing promise as a biomarker or prognostic factor as well as a potential therapeutic target. This review focuses on recent work addressing the role of CCN4 in cancer. While CCN4 has been identified as an oncogene in a number of cancers, where it enhances cell migration and promoting epithelial–mesenchymal transition, there are other cancers where CCN4 appears to play an inhibitory role. The mechanisms underlying these differences in cellular response have not yet been delineated, but are an active area of investigation. The expression and activities of CCN4 splice variants are likewise an emerging area for study. CCN4 acts as an autocrine factor that regulates the cancer cells from which it is secreted. However, CCN4 is also a paracrine factor that is secreted by stromal fibroblasts, and can affect the function of vascular endothelial cells. In summary, current evidence is abundant in regard to establishing potential roles for CCN4 in oncogenesis, but much remains to be learned about the functions of this fascinating protein as both an autocrine and paracrine regulator in the tumor microenvironment.

Keywords: matricellular proteins, oncogenesis, extracellular matrix, tumor microenvironment, signal transduction

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