The role of CCNs in controlling cellular communication in the tumor microenvironment

Abstract

The Cellular communication network (CCN) family of growth regulatory factors comprises six secreted matricellular proteins that promote signal transduction through cell-cell or cell-matrix interaction. The diversity of functionality between each protein is specific to the many aspects of healthy and cancer biology. For example, CCN family proteins modulate cell adhesion, proliferation, migration, invasiveness, apoptosis, and survival. In addition, the expression of each protein regulates many biological and pathobiological processes within its microenvironment to regulate angiogenesis, inflammatory response, chondrogenesis, fibrosis, and mitochondrial integrity. The collective range of CCN operation remains fully comprehended; however, understanding each protein's microenvironment may draw more conclusions about the abundance of interactions and signaling cascades occurring within such issues. This review observes and distinguishes the various roles a CCN protein may execute within distinct tumor microenvironments and the biological associations among them. Finally. We also review how CCN-family proteins can be used in nano-based therapeutic implications.

The role of yes activated protein (YAP) in melanoma metastasis

“…The CCN family of matricellular proteins have attracted interest due to their roles in modulating fibrosis and cancer progression, for reviews see. 100 , 101 Including in melanoma cells, CCN1 and CCN2 expression is induced by TGFβ, RAS/MEK/ERK, hypoxia and mechanotransduction; indeed, they are considered prototypical YAP targets. 13 , 14 , 102 , 103 , 104 , 105 , 106 , 107 CCN1 and CCN2 are pro-adhesive and signal through a variety of integrin heterodimers to promote angiogenic and ECM programs in vivo and in vitro .…”

CCN proteins: opportunities for clinical studies—a personal perspective

“…Other nanodelivery methods and formulations can be found in the literature and are being actively pursued. The review by Birkeness et al (2023) on CCN5 offers some of these. In addition, as described by Eguchi et al (2023) it may be possible to construct exosome nanocarriers for delivery of CCN proteins utilizing patient mesenchymal stem cells for production of exosomes and then modified for precision targeting and no off-target effects (Hades et al., 2021).…”

“…Understanding the regulation of CCN5 could lead to development of new treatment strategies for obesity and metabolic diseases as well as serve as a target in regenerative medicine. To this end in a recent review by Birkeness et al (2023) in the Banerjee group on how CCNs control communication in the tumor microenvironment they described potential nanotechnology approaches for CCN5 delivery. They described PEG‐protein conjugates, encapsulation of CCN5 protein in polymeric vesicles (polymersome) and CCN5 layered gold nanoparticles.…”

Inception and establishment of the International CCN Society (ICCNS) and of the Journal of Cell Communication and Signaling (JCCS): A response to A. Leask’s Editorial entitled "Modeling the microenvironment special issue"

“…This present response highlights key references, taken among the 154 reviews and 1255 articles citing CCN on PubMed: Brigstock,1999; Brigstock et al 2003, Bork 1993; Birkeness, 2022; Giusti and Scotlandi 2021; Joliot et al 1992; Krupska et al 2015; Kubota et al 2022; Lau and Lam 1999; Lau 2016; Perbal 1994; Perbal 2001; Perbal 2004; Perbal 2013; Perbal and Perbal 2016; Perbal 2018; Perbal et al 2018; Tran 2018; Twigg 2018; Weiskirchen 2011; Yeger and Perbal 2021). Notably, this wealth of scientific achievements and contribution to the scientific literature has rested on the initial efforts made by those recognized herein who established the ICCNS and JCCS.…”