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CCN proteins: opportunities for clinical studies-a personal perspective.

ABSTRACT: The diverse members of the CCN family now designated as CCN1(CYR61), CCN2 (CTGF), CCN3(NOV), CCN4(WISP1), CCN5(WISP2), CCN6(WISP3) are a conserved matricellular family of proteins exhibiting a spectrum of functional properties throughout all organs in the body. Interaction with cell membrane receptors such as integrins trigger intracellular signaling pathways. Proteolytically cleaved fragments (constituting the active domains) can be transported to the nucleus and perform transcriptional relevant functional activities. Notably, as also found in other protein families some members act opposite to others creating a system of functionally relevant checks and balances. It has become apparent that these proteins are secreted into the circulation, are quantifiable, and can serve as disease biomarkers. How they might also serve as homeostatic regulators is just becoming appreciated. In this review I have attempted to highlight the most recent evidence under the subcategories of cancer and non-cancer relevant that could lead to potential therapeutic approaches or ideas that can be factored into clinical advances. I have added my own personal perspective on feasibility.

SUBMITTER: Yeger H

PROVIDER: S-EPMC10326213 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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CCN proteins: opportunities for clinical studies-a personal perspective.

Yeger Herman H

Journal of cell communication and signaling 20230517 2

The diverse members of the CCN family now designated as CCN1(CYR61), CCN2 (CTGF), CCN3(NOV), CCN4(WISP1), CCN5(WISP2), CCN6(WISP3) are a conserved matricellular family of proteins exhibiting a spectrum of functional properties throughout all organs in the body. Interaction with cell membrane receptors such as integrins trigger intracellular signaling pathways. Proteolytically cleaved fragments (constituting the active domains) can be transported to the nucleus and perform transcriptional relevan ...[more]

PMID: 37195381

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Project description:The CCN family of proteins is composed of six members, which are now well recognized as major players in fundamental biological processes. The first three CCN proteins discovered were designated CYR61, CTGF, and NOV because of the context in which they were identified. Both CYR61 and CTGF were discovered in normal cells, whereas NOV was identified in tumors. Soon after their discovery, it was established that they shared important and unique structural features and distinct biological properties. Based on these structural considerations, the three proteins were proposed to belong to a family that was designated CCN by P. Bork. Hence the CCN1, CCN2 and CCN3 acronyms. The family grew to six members a few years later with the description of three proteins WISP-1, WISP-2 and WISP-3 (CCN4, CCN5 and CCN6), that shared the same tetramodular and conserved structural features. With the functions of the CCN proteins being uncovered, this raised a nomenclature problem. A scientific committee convened in Saint Malo (France) proposed to apply the CCN nomenclature to the six members of the family. Although the unified nomenclature was proposed in order to avoid serious misconceptions and lack of precision associated with the use of the old acronyms, the acceptance of the new acronyms has taken time. In order to evaluate how the use of disparate nomenclatures have had an impact on the CCN protein field, we conducted a survey of the articles that have been published in this area since the discovery of the first CCN proteins and inception of the field. We report in this manuscript the confusion and serious deleterious scientific consequences that have stemmed from a disorganized usage of several unrelated acronyms. The conclusions that we have reached call for a unification that needs to overcome personal habits and feelings. Instead of allowing the CCN field to fully crystalize and gain the recognition that it deserves the usage of many different acronyms represents a danger that everyone must fight against in order to avoid its deliquescence. We hope that the considerations discussed in the present article will encourage all authors working in the CCN field to work jointly and succeed in building a strong and coherent CCN scientific community that will benefit all of us.

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CCN proteins: opportunities for clinical studies-a personal perspective.

Publications

CCN proteins: opportunities for clinical studies-a personal perspective.

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