Therapeutic potential of cysteine-rich protein 61 in rheumatoid arthritis

Xu, Tao; He, Yinghua; Wang, Mingquan; Yao, Hongwei; Ni, Ming-ming; Zhang, Lei; Meng, Xiao‐Ming; Huang, Cheng; Ge, Yunxuan; Li, Jun

doi:10.1016/j.gene.2016.07.053

Cited by 14 publications

(6 citation statements)

References 69 publications

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“…with hormone-dependent breast cancer including angiogenesis (7,10); however, the alteration of Cyr61 expression has been demonstrated to be associated with a number of pathologies (11)(12)(13), including malignant neoplasms (14,15). In previous studies by our group, Cyr61 expression profiling in BC and its functional expression regulation was examined (16,17) demonstrating a stage-dependent induction of Cyr61 in BC tumorigenesis and hypoxia-induced alternative splicing of Cyr61 in tumor cells.…”

Section: Clinical Relevance Of Cyr61 Expression In Patientsmentioning

confidence: 97%

Clinical relevance of Cyr61 expression in patients with hormone-dependent breast cancer

et al. 2017

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Abstract. Tumor resistance to endocrine therapy triggers estrogen-independent cancer progression, which is a major obstacle to the successful treatment of hormone receptor positive breast cancer (BC). The underlying molecular mechanisms of endocrine resistance are not fully understood yet. The matricellular protein cysteine-rich angiogenic inducer 61 (Cyr61) is associated with tumor invasiveness and the induction of tumorigenesis in various malignancies in vivo and the induction of estrogen-independence and endocrine therapy resistance in BC. The present study evaluated the potential effects and clinical relevance of Cyr61 expression levels in 67 patients with primary non-metastatic BC. Immunohistochemical analysis of formalin-fixed paraffin-embedded tissue sections was performed, and the association between Cyr61 protein expression and clinicopathological factors and survival was analyzed. Cyr61 overexpression was revealed to be significantly associated with a positive estrogen receptor (ER)/progesterone receptor (PR) status (P=0.016) and to the molecular subtype of BC (P=0.039). Compared with patients without Cyr61 overexpression, patients with Cyr61 overexpression exhibited an increased recurrence rate (30.6 vs. 22.6%) and decreased long-term survival (10-year overall survival, 62.9 vs. 69.7%); however, these associations did not reach statistically significant levels in Cox regression model analysis. Similar results were identified in the subgroup analysis of patients with ER/PR positive BC. These results indicate that Cyr61 serves a role in the development of endocrine therapy resistance in BC and is thus a potential therapeutic target to overcome endocrine therapy resistance. However, additional long-term survival analyses with large patient populations are required.

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Section: Clinical Relevance Of Cyr61 Expression In Patientsmentioning

confidence: 97%

Clinical relevance of Cyr61 expression in patients with hormone-dependent breast cancer

et al. 2017

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“…Much cellular and preclinical evidence has suggested that modulating CCN1 expression in RA disease has therapeutic potential [ 49 ]. Promising experimental findings suggest the feasibility of designing peptide-based vaccination against RA.…”

Section: Ccn1 In Ra and Oamentioning

confidence: 99%

Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis

MacDonald

Huang

Liu

et al. 2021

IJMS

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The CCN family of matricellular proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1-2-3/CCN4-5-6) are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation. These proteins are well recognized for their important roles in many cellular processes, including cell proliferation, adhesion, migration and differentiation, as well as the regulation of extracellular matrix differentiation. Substantial evidence implicates four of the proteins (CCN1, CCN2, CCN3 and CCN4) in the inflammatory pathologies of rheumatoid arthritis (RA) and osteoarthritis (OA). A smaller evidence base supports the involvement of CCN5 and CCN6 in the development of these diseases. This review focuses on evidence providing insights into the involvement of the CCN family in RA and OA, as well as the potential of the CCN proteins as therapeutic targets in these diseases.

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“…Cyr61 mediates cell proliferation, adhesion, migration, and differentiation. The role of Cyr61 has been extensively studied in tumour biology and is also considered important for RA [6,7]. Cyr61 is stimulated by interleukin-17 (IL-17) and in turn, promotes FLS proliferation, thus contributing to the hyperplasia of synoviocytes [8].…”

Section: Introductionmentioning

confidence: 99%

CYR61 synthesis is Induced by Interleukin-6 and Promotes Migration and Invasion of Fibroblast-like Synoviocytes in Rheumatoid Arthritis

Choi

Jeong

Ghang

et al. 2020

Preprint

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Background:Interleukin-6 (IL-6) is involved in fibroblast-like synoviocyte (FLS) activation and promotes pannus formation and bone and cartilage destruction in rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61) protein regulates cell proliferation, migration, and differentiation. The aim of this study was to investigate the role of Cyr61 in RA-FLS migration and invasion after IL-6 stimulation. Methods:Western blotting and reverse transcription-polymerase chain reaction were used to examine protein and mRNA levels of Cyr61, matrix metalloproteinases (MMPs), and other signalling proteins. Knockdown of gene expression was performed with siRNA, and RNA sequencing was performed for differential gene analysis. Migration and invasion were assessed by wound healing and Boyden chamber assays. Results:Cyr61 levels were elevated in FLSs from RA patients compared to those in osteoarthritis patients. Control and IL-6-treated FLSs showed differential gene expression. IL-6 stimulated protein synthesis of Cyr61, which was attenuated by the extracellular signal-related kinase 1/2 (ERK 1/2) inhibitor, PD98059, and knockdown of early growth response 3 (EGR3), but not of JUN. IL-6-induced Cyr61 protein synthesis increased expression of MMP2. Cyr61 promoted FLS migration and invasion in an autocrine manner. Knockdown of CYR61 and a neutralizing antibody attenuated Cyr61 synthesis and IL-6 induced FLS migration. Conclusions:By modulating the ERK/EGR3 pathway, IL-6 stimulated Cyr61 production and in turn increasedinvasiveness of FLS. Our data suggest that Cyr61 might be a potential target to prevent the progression of joint damage in RA.

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Therapeutic potential of cysteine-rich protein 61 in rheumatoid arthritis

Cited by 14 publications

References 69 publications

Clinical relevance of Cyr61 expression in patients with hormone-dependent breast cancer

Clinical relevance of Cyr61 expression in patients with hormone-dependent breast cancer

Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis

CYR61 synthesis is Induced by Interleukin-6 and Promotes Migration and Invasion of Fibroblast-like Synoviocytes in Rheumatoid Arthritis

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