Expression of Cyr61 (CCN1) in human oral squamous cell carcinoma: An independent marker for poor prognosis

Kok, Sang‐Heng; Chang, Hao-Hueng; Tsai, Ju-Yi; Hung, Hsin-Chia; Lin, Chungwei; Chiang, Chun-Pin; Liu, Cheing-Meei; Kuo, Mark Yen‐Ping

doi:10.1002/hed.21381

Cited by 33 publications

(25 citation statements)

References 38 publications

(46 reference statements)

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“…Several of these 11 genes have already been associated with cancer progression. For example, Cyr61 has been associated with poor prognosis in squamous cell cancers of the head and neck (25) and esophagus (26). CCR2 has been linked to breast cancer metastasis (27).…”

Section: Discussionmentioning

confidence: 99%

C-C Chemokine Receptor 5 on Pulmonary Mesenchymal Cells Promotes Experimental Metastasis via the Induction of Erythroid Differentiation Regulator 1

Mango

West

et al. 2014

Molecular Cancer Research

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C-C Chemokine receptor five knockout (Ccr5-/-) mice develop fewer experimental pulmonary metastases than wild type (WT) mice. This phenomenon was explored by applying gene-expression profiling to the lungs of mice with these metastases. Consequently, Erythroid Differentiation Regulator 1 (Erdr1) was identified as upregulated in the WT mice. Though commonly associated with bone marrow stroma, Erdr1 was differentially expressed in WT pulmonary mesenchymal cells (PMCs) and murine embryonic fibroblasts (MEFs). Moreover, the Ccr5 ligand Ccl4 increased its expression by 3.36 ± 0.14 fold. Ccr5 signaling was dependent on the Map2k but not the Pi3k pathway since treatment with U0126 inhibited upregulation of Erdr1 but treatment with LY294002 increased the expression by 3.44 ± 0.92 fold (p < 0.05). Erdr1's effect on B16-F10 melanoma metastasis was verified by the adoptive transfer of WT MEFs into Ccr5-/- mice. In this model, MEFs that had been transduced with Erdr1 shRNA lowered metastasis by 33% compared to control transduced MEFs. The relevance of ERDR1 on human disease was assessed by co-culturing chronic lymphocytic leukemia (CLL) cells with M2-10B4 stromal cells that had been transfected with shRNA or control plasmids. After 96 hours of co-culture, the cell counts were higher with control cell lines compared with Erdr1 knockdown lines (OR 1.88 ± 0.27, 2.52 ± 0.66 respectively). This increase was associated with a decrease in apoptotic cells (OR 0.69 ± 0.18, 0.58 ± 0.12 respectively). Implications Therefore, ERDR1 is a stromal-derived factor that promotes cancer cell survival in vitro and in an experimental metastasis model.

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Section: Discussionmentioning

confidence: 99%

C-C Chemokine Receptor 5 on Pulmonary Mesenchymal Cells Promotes Experimental Metastasis via the Induction of Erythroid Differentiation Regulator 1

Mango

West

et al. 2014

Molecular Cancer Research

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“…In addition to angiogenesis, CCN1 can also promote cancer cell proliferation, invasion, survival, and metastasis [74,75,141]. Accordingly, subsequent studies have shown that forced expression of CCN1 enhanced tumor growth in xenografts of breast cancer cells [142], prostate cancer cells [74], ovarian carcinoma cells [78], and squamous carcinoma cells [143]. Consistently, silencing of CCN1 expression decreased tumor growth in xenografts of prostate cancer cells [74] and pancreatic cancer cells [144].…”

Section: Ccn1 In Pathologiesmentioning

confidence: 99%

“…The clinical relevance of these observations is supported by the finding of a significant correlation between CCN1 expression and the stage, tumor size, lymph node positivity, and poor prognosis in several cancers, including breast cancer [142,145–148], prostate cancer [149], glioma [150], gastric adenocarcinoma [151], and squamous cell carcinoma [143]. In MCF7 breast cancer cells, which are dependent on estrogen for growth, overexpression of CCN1 renders these cells estrogen-independent and significantly resistant to apoptosis, in part through upregulation of the anti-apoptotic protein XIAP [81,152,153].…”

Section: Ccn1 In Pathologiesmentioning

confidence: 99%

CCN1/CYR61: the very model of a modern matricellular protein

Lau

2011

Cell. Mol. Life Sci.

274

377

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CCN1 (CYR61) is a dynamically expressed, multifunctional matricellular protein that plays essential roles in cardiovascular development during embryogenesis, and regulates inflammation, wound healing and fibrogenesis in the adult. Aberrant CCN1 expression is associated with myriad pathologies, including various cancers and diseases associated with chronic inflammation. CCN1 promotes diverse and sometimes opposing cellular responses, which can be ascribed, as least in part, to disparate activities mediated through its direct binding to distinct integrins in different cell types and contexts. Accordingly, CCN1 promotes cell proliferation, survival and angiogenesis by binding to integrins αvβ3, and induces apoptosis and senescence through integrin α6β1 and heparan sulfate proteoglycans. The ability of CCN1 to trigger the accumulation of a robust and sustained level of reactive oxygen species underlies some of its unique activities as a matrix cell-adhesion molecule. Emerging studies suggest that CCN1 might be useful as a biomarker or therapeutic target in certain diseases.

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“…In fact, the increased presence of one or multiple members of the CCN family is associated with poor prognosis in breast, prostate, pancreatic, renal, bone, head and neck, and brain cancers (186–190). More specifically, CCN4 is upregulated in early stages of prostate cancer and correlated with higher circulating levels of the protein (191).…”

Section: Introductionmentioning

confidence: 99%

Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization

Sawyer

Kyriakides

2016

Advanced Drug Delivery Reviews

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Extracellular matrix is composed by a complex array of molecules that together provide structural and functional support to cells. These properties are mainly mediated by the activity of collagenous and elastic fibers, proteoglycans, and proteins such as fibronectin and laminin. ECM composition is tissue-specific and could include matricellular proteins whose primary role is to modulate cell-matrix interactions. In adults, matricellular proteins are primarily expressed during injury, inflammation and disease. Particularly, they are closely associated with the progression and prognosis of cardiovascular and fibrotic diseases, and cancer. This review aims to provide an overview of the potential use of matricellular proteins in drug delivery including the generation of therapeutic agents based on the properties and structures of these proteins as well as their utility as biomarkers for specific diseases.

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Expression of Cyr61 (CCN1) in human oral squamous cell carcinoma: An independent marker for poor prognosis

Abstract: Cyr61 is a positive growth modulator of oral SCC and Cyr61 overexpression is an independent prognostic indicator for patients with oral SCC.

Cited by 33 publications

References 38 publications

C-C Chemokine Receptor 5 on Pulmonary Mesenchymal Cells Promotes Experimental Metastasis via the Induction of Erythroid Differentiation Regulator 1

C-C Chemokine Receptor 5 on Pulmonary Mesenchymal Cells Promotes Experimental Metastasis via the Induction of Erythroid Differentiation Regulator 1

CCN1/CYR61: the very model of a modern matricellular protein

Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization

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