Emerging role of CCN family proteins in tumorigenesis and cancer metastasis (Review)

Li, Jun; Ye, Lin; Owen, Sioned; Weeks, Hoi Ping; Zhang, Zhongtao; Jiang, Wen Guo

doi:10.3892/ijmm.2015.2390

Cited by 104 publications

(98 citation statements)

References 133 publications

(151 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 99%

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

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

Section: Clinical Relevance Of Cyr61 Expression In Patientsmentioning

confidence: 99%

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

et al. 2017

View full text Add to dashboard Cite

show abstract

“…CCN1 overexpression is associated with the progression of various tumors, including prostate cancer, breast cancer, glioma, colorectal cancer, and osteosarcoma, through its ability to promote angiogenesis, cell migration or proliferation [28, 29]. In contrast to in cardiomyocytes, overexpression of CCN1in human breast cancer MCF-7 cells upregulates XIAP expression to promote chemoresistance to paclitaxel, Adriamycin, and β-lapachone through integrin α v β 3 /α v β 5 and NFκB signaling pathway [30].…”

Section: Discussionmentioning

confidence: 99%

Matricellular protein CCN1 mediates doxorubicin-induced cardiomyopathy in mice

Hsu

2016

Oncotarget

View full text Add to dashboard Cite

Doxorubicin (DOX) is an effective chemotherapeutic agent however its clinical use is limited by its cumulative cardiotoxicity. Matricellular protein CCN1 mediates work-overload-induced cardiac injury. We aimed to assess the role of CCN1 in DOX-associated cardiomyopathy. Here we discovered CCN1 expression in the myocardium 1 day after DOX treatment (15 mg/kg; i.p.) in mice. Whereas CCN1 synergizes with Fas ligand (FasL) to induce cardiomyocyte apoptosis, we found that FasL was also induced by DOX in the heart. To assess the function of CCN1 in vivo, knockin mice (Ccn1dm/dm) expressing an β6β1-binding defective CCN1 mutant were treated with a single dose of DOX (15 mg/kg; i.p.). Compared with wild-type mice, Ccn1dm/dm mice were resistant to DOX-induced cardiac injury and dysfunction 14 days after injection. Using rat cardiomyoblast H9c2 cells, we demonstrated that DOX induced reactive oxygen species accumulation to upregulate CCN1 and FasL expression. CCN1 mediated DOX cardiotoxicity by engaging integrin β6β1 to promote p38 mitogen-activated protein kinase activation and the release of mitochondrial Smac and HtrA2 to cytosol, thereby counteracting the inhibition of XIAP and facilitating apoptosis. In summary, CCN1 critically mediates DOX-induced cardiotoxicity. Disrupting CCN1/β6β1 engagement abolishes DOX-associated cardiomyopathy in mice.

show abstract

“…CYR61 is known to have a variety of binding partners (receptors), such as integrins, IGFs, VEGF, LDL receptor proteins, TGF‐β, and heparan sulfate proteoglycans. CYR61 is involved in a vast number of signaling pathways that regulate tumorigenesis, angiogenesis, inflammation, and wound repair (17). Moreover, Cyr61 has been known for decades to play a role in chondrocyte maturation and cartilage development that contributes to the development of the mammalian embryonic skeleton (18, 19).…”

mentioning

confidence: 99%

Cysteine‐rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling

Yang

Wang

et al. 2018

FASEB j.

View full text Add to dashboard Cite

Emerging evidence suggests that cysteine-rich protein 61 (CYR61) plays a role in the differentiation and development of chondrocytes, osteoblasts, and osteoclasts; however, little is known about its role in adipogenesis. The current study indicates that the expression level of Cyr61 was altered in primary cultured marrow stromal cells and the established mesenchymal cell line, C3H10T1/2, after adipogenic treatment. Overexpressing Cyr61 repressed C3H10T1/2 and primary marrow stromal cells to differentiate into mature adipocytes. Conversely, inhibition of endogenous Cyr61 induced C3H10T1/2 and primary marrow stromal cells to fully differentiate. Mechanism investigations reveal that knockdown of Cyr61 inhibited the nuclear translocation of β-catenin and decreased nuclear protein levels of β-catenin and transcription factor 7-like 2. Moreover, the silencing of Cyr61 increased protein levels of phosphorylated ribosomal protein S6 kinase B1, mammalian target of rapamycin, eukaryotic translation initiation factor 4E-binding protein 1, and ribosomal protein S6-the major components of mammalian target of rapamycin complex 1 (mTORC1) signaling-in C3H10T1/2 cells. Additional investigations demonstrated that treatment with rapamycin significantly attenuated adipocyte formation that was induced by Cyr61 small interfering RNA (siRNA) transfection. Moreover, Cyr61 siRNA also lost its ability to stimulate adipocyte formation under the background of β-catenin overexpression. Taken together, our study provides evidence that CYR61 regulates adipocyte differentiation via multiple signaling pathways that involve at least the inactivation of mTORC1 signaling and the activation of canonical Wnt signaling.-Yang, Y., Qi, Q., Wang, Y., Shi, Y., Yang, W., Cen, Y., Zhu, E., Li, X., Chen, D., Wang, B. Cysteine-rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling.

show abstract

Emerging role of CCN family proteins in tumorigenesis and cancer metastasis (Review)

Cited by 104 publications

References 133 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

Matricellular protein CCN1 mediates doxorubicin-induced cardiomyopathy in mice

Cysteine‐rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling

Contact Info

Product

Resources

About