The role of the CCN family of proteins in blood cancers

Since the authors first reviewed this subject in 2016 significant progress has been documented in the CCN field with advances made in the understanding of how members of the CCN family of proteins, CCN1‐6, contribute to the pathogenesis and progression, positive and negative, of a larger variety of cancers. As termed matricellular proteins, and more recently the connective communication network, it has become clearer that members of the CCN family interact complexly with other proteins in the extracellular microenvironment, membrane signaling proteins, and can also operate intracellularly at the transcriptional level. In this review we expand on this earlier information providing new detailed information and insights that appropriate a much greater involvement and importance of their role in multiple aspects of cancer. Despite all the new information many more questions have been raised and intriguing results generated that warrant greater investigation. In order to permit the reader to smoothly integrate the new information we discuss all relevant CCN members in the context of cancer subtypes. We have harmonized the nomenclature with CCN numbering for easier comparisons. Finally, we summarize what new has been learned and provide a perspective on how our knowledge about CCN1‐6 is being used to drive new initiatives on cancer therapeutics.

Section: Lymphoma and Leukemiasmentioning

confidence: 99%

The CCN axis in cancer development and progression

Yeger

Perbal²

2021

“…CCN1, a matricellular protein is involved in stem cell signalling within the haematopoietic microenvironment (McCallum and Irvine 2009; Wells et al 2015) and has been associated with a number of haematological malignancies including acute myeloid leukaemia (AML) and multiple myeloma (MM) (Crawford and Irvine 2016). CCN1, also known as CYR61, belongs to CCN family of proteins that are comprised of a signal peptide (SP), Insulin like growth factor binding domain (IGFBP), Von Willebrand type C repeat (VWC), a hinge region leading to the Thrombospondin type I domain (TSP‐1) and cysteine rich carboxyl terminal (CT) (Planque and Perbal 2003).…”

Section: Ccn1 (Cyr61)mentioning

confidence: 99%

Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

Zaidi

Dresman²,

Burt³

et al. 2018

Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin's lymphoma characterised by overexpression of cyclin D1. Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease with median survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators in progressive MCL. We have used the human MCL cell lines REC1 < G519 < JVM2 as a model for disease aggression. The magnitude of CCN1 expression in human MCL cells is REC1 > G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1 expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expression of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18-20 and 28-30 kDa) decreased with disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21 CIP1 and p27 KIP1) are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519 cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27 KIP1 followed a similar profile of expression as cyclin D1. Conversely, p21 CIP1 was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellular localization detected p21 CIP1 / p27 KIP1 primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction with reduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease and treatment resistance.

“…Another major target regarding the pathological significance of CCN2 research is tumor development and metastasis. Detailed advances in this field are described in recent review articles (Kubota and Takigawa 2015; Riser et al 2015; Yeger and Perbal 2016; Wells et al 2015); and numerous papers have appeared, including those on colorectal cancer (Ubink et al 2016), breast cancer (Kleer 2016), pancreatic cancer (Banerjee et al 2016), and blood cancers (Crawford and Irvine 2016). Other pathological events of significance such as inflammation, diabetic nephropathy, and diabetic retinopathy, have been described in a variety of reviews (Kubota and Takigawa 2007a; Kubota and Takigawa 2015; Wang et al 2015; Klaassen et al 2015).…”

Section: After the Public Announcement Of The Ccn Nomenclaturementioning

confidence: 99%

An early history of CCN2/CTGF research: the road to CCN2 via hcs24, ctgf, ecogenin, and regenerin

Takigawa

2017

The principal aim of this historical review is to present the processes by which the different aspects of CCN2/CTGF/Hcs24 were discovered by different groups and how much CCN2/CTGF, by being integrated into CCN family, has contributed to the establishment of the basic concepts regarding the role and functions of this new class of proteins. This review should be particularly useful to new investigators who have recently entered this exciting field of study and also provides a good opportunity to acknowledge the input of those individuals who participated in the development of this scientific field.