Nephroblastoma Overexpressed/Cysteine-Rich Protein 61/Connective Tissue Growth Factor/Nephroblastoma Overexpressed Gene-3 (NOV/CCN3), a Selective Adrenocortical Cell Proapoptotic Factor, Is Down-Regulated in Childhood Adrenocortical Tumors

Doghman, Mabrouka; Arhatte, Malika; Thibout, Hélène; Rodrigues, Giovanna Assis; Moura, Juliana de; Grosso, Sébastien; West, Alina Nico; Laurent, M.; Mas, J.-C.; Bongain, A.; Zambetti, Gerard P.; Figueiredo, Bonald C.; Auberger, Patrick; Martinerie, Cécile; Lalli, Enzo

doi:10.1210/jc.2007-0342

Cited by 54 publications

(48 citation statements)

References 35 publications

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“…Integrin receptor-dependent signaling pathways may activate P38/MAPK and JNK/MAPK, thereby promoting the phosphorylation of Bcl-2, the expression of Bax and induce the apoptosis of tumor cells (33,34). Moreover, previous findings have shown that NOV induced cell apoptosis or growth inhibition in many types of cancer through activation of the MAPK signaling pathway (35,36). Therefore, we detected the effects of NOV on the MAPK signaling pathway in osteosarcoma cell lines.…”

Section: Discussionmentioning

confidence: 97%

NOV inhibits proliferation while promoting apoptosis and migration in osteosarcoma cell lines through p38/MAPK and JNK/MAPK pathways

et al. 2015

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Abstract. The nephroblastoma overexpressed (NOV) gene, a member of the CCN gene family that encodes secreted proteins involved in a variety of processes including tumorigenesis, is often altered in a variety of tumors, including osteosarcoma. Recent studies indicated that NOV promotes osteosarcoma metastasis, but its biological functions and molecular mechanisms on osteosarcoma proliferation have yet to be fully elucidated. The aim of the present study was to examine the role of NOV in osteosarcoma biology. Reverse transcriptionpolymerase chain reaction (RT-PCR) and western blot analysis were performed to characterize the endogenous expression of NOV in osteosarcoma cell lines. Recombinant adenovirus expressing NOV/siNOV (AdNOV/AdsiNOV) was used to infect osteosarcoma cell lines with a relatively low/high endogenous NOV expression to determine the functional relevance of NOV expression to osteosarcoma cell growth and migration in vitro, respectively. As a result, osteosarcoma cell proliferation was significantly reduced by NOV upregulation, indicated by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltrazolium bromide (MTT), colony forming assay and cell cycle analysis. Cell apoptosis was markedly induced, as indicated by Hoechst 33258 staining assay and flow cytometry (FCM) detection. Despite the antiproliferative effect, NOV-transfected osteosarcoma cells exhibited increased migration ability. The possible molecular mechanisms underlying the biological role of NOV were also investigated. The results demonstrated that NOV increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK) mitogen-actived protein kinases (MAPKs) in osteosarcoma cell lines. When the phosphorylation of p38 and JNK were inhibited by SB203580 (p38 inhibitor) or SP600125 (JNK inhibitor), respectively, the NOV-induced proliferation inhibition and cell apoptosis were reversed. In conclusion, the results revealed that NOV regulates the tumor growth of osteosarcoma cells through activation of the MAPK signaling pathway and promotes osteosarcoma cell migration in vitro.

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Section: Discussionmentioning

confidence: 97%

NOV inhibits proliferation while promoting apoptosis and migration in osteosarcoma cell lines through p38/MAPK and JNK/MAPK pathways

et al. 2015

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“…The functions of CCN3 protein among these different tissues are, however, different. CCN3 was originally described as antiproliferative (3), and its expression was associated with differentiation of Wilms' tumor (4), rhabdomyosarcomas (6), neuroblastomas (7), cartilaginous tumors (8), adrenocortical tumors (9) and with inhibition of the growth and decrease in tumorigenicity of several tumor cell lines including glioblastoma (10), choriocarcinoma (11) and Ewing's sarcoma (12). Furthermore, CCN3 expression was correlated with the increased proliferative index of 3T3 fibroblast (13) and tissue samples of the prostate (14).…”

Section: Introductionmentioning

confidence: 99%

CCN3 (NOV) regulates proliferation, adhesion, migration and invasion in clear cell renal cell carcinoma

Liu

et al. 2012

Oncology Letters

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Abstract. The CCN3/nephroblastoma overexpressed gene belongs to the CCN family of genes that encode secreted proteins involved in a variety of processes including tumorigenesis. Altered expression of CCN3 has been observed in human nephroblastoma and renal cell carcinoma (RCC), suggesting that CCN3 plays a role in kidney tumorigenesis. The aim of the present study was to examine the role of CCN3 in clear cell RCC biology. In particular, we studied the expression of CCN3 in 32 pairs of RCC tissues and corresponding normal kidney tissues using immunohistochemistry. The CCN3 gene was transfected into the 786-O cell line and the behaviors of stably transfected clones were analyzed. Results showed the expression of CCN3 was lower in RCC tissues compared to corresponding normal kidney tissues and the expression of CCN3 was inversely correlated with the Ki67 index. CCN3-expressing clones exhibited significantly inhibited cell proliferation. Furthermore, CCN3-transfected 786-O cells exhibited increased adhesion to extracellular matrix proteins, migration and invasion in Matrigel. Our data indicated that CCN3 plays an anti-proliferative role in clear cell RCC cells and promotes the adhesion, migration and invasion of clear cell RCC cells. IntroductionRenal cell carcinoma (RCC) is the most common type of cancer of the kidney. Metastasis frequently becomes evident at the time of diagnosis or patients develop distant metastases following removal of the primary tumor. The treatment of metastatic, locally unresectable RCCs remains a challenge for urologists (1). There is a great need to understand the basic biology of RCC and develop better therapeutic options.The CCN3 (nephroblastoma overexpressed, NOV) gene belongs to the CCN family of genes, which has five additional members: cystein-rich protein 61 (Cyr61), connective tissue growth factor (CTGF), Wnt-1-induced secreted protein (WISP)-1, WISP-2 and WISP-3. CCN proteins are involved in fundamental biological processes such as cell proliferation, attachment, migration, differentiation, wound healing, angiogenesis and tumorigenesis (2).The CCN3 protein is detectable at varying levels in the kidney, muscle, cartilage, brain, lung, ovary and heart (3-5). The functions of CCN3 protein among these different tissues are, however, different. CCN3 was originally described as antiproliferative (3), and its expression was associated with differentiation of Wilms' tumor (4), rhabdomyosarcomas (6), neuroblastomas (7), cartilaginous tumors (8), adrenocortical tumors (9) and with inhibition of the growth and decrease in tumorigenicity of several tumor cell lines including glioblastoma (10), choriocarcinoma (11) and Ewing's sarcoma (12). Furthermore, CCN3 expression was correlated with the increased proliferative index of 3T3 fibroblast (13) and tissue samples of the prostate (14). Although CCN3 reduced the growth rate of Ewing's sarcoma transfectants ex vivo, CCN3 expression was associated with poor prognosis and shown to increase cell motility, resulting in enhanced metastatic potential ...

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“…Initially discovered from myeloblastosis-associated virus-induced nephroblastoma, the molecule also shares some homology with the IGFBP family (11). Although the functions of NOV/CCN3 are not clear, it has been suggested that the molecule is a keen regulator of haematopoietic stem cells and is associated with tumourigenicity in animal models (12).…”

Section: Discussionmentioning

confidence: 99%

Pattern of expression of CCN family members Cyr61, CTGF and NOV in human acute and chronic wounds

Minhas

Martin

Ruge

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. The CCN family is a group of extremely cysteinerich proteins that are found within the extracellular matrix and are comprised of cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN 2) and nephroblastoma overexpressed (NOV/CCN3). Collectively, these proteins stimulate mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration, and regulate angiogenesis, tumour growth, placentation, implantation, embryogenesis and endochondral ossification. Despite such diverse activity, CCN protein function has not been explored in human wounds and healing. In the present study, we investigated the expression of these proteins in samples of normal, acute and chronic wounds using immunohistochemical staining and real-time quantitative RT-PCR. Statistical analysis was performed using the Fisher's exact test. Our results showed that, although all CCN proteins were present in normal, acute and chronic wounds, their expression levels differed, particularly in the case of connective tissue growth factor (CTGF), for which significantly reduced levels were found in chronic wounds compared to acute wounds (p<0.002). Thus, the lack of CTGF in wound tissues may contribute to the abnormal healing of clinical wounds. This suggests that CCN proteins may play an important role in human tissue wound healing. This further suggests that human wound healing may be promoted by manipulating the levels of this protein.

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Nephroblastoma Overexpressed/Cysteine-Rich Protein 61/Connective Tissue Growth Factor/Nephroblastoma Overexpressed Gene-3 (NOV/CCN3), a Selective Adrenocortical Cell Proapoptotic Factor, Is Down-Regulated in Childhood Adrenocortical Tumors

Cited by 54 publications

References 35 publications

NOV inhibits proliferation while promoting apoptosis and migration in osteosarcoma cell lines through p38/MAPK and JNK/MAPK pathways

NOV inhibits proliferation while promoting apoptosis and migration in osteosarcoma cell lines through p38/MAPK and JNK/MAPK pathways

CCN3 (NOV) regulates proliferation, adhesion, migration and invasion in clear cell renal cell carcinoma

Pattern of expression of CCN family members Cyr61, CTGF and NOV in human acute and chronic wounds

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