Cyr61 Expression is associated with prognosis in patients with colorectal cancer

Jeong, Dongjun; Heo, Su‐Hak; Ahn, Tae Sung; Lee, Sook-Young; Park, Soyoung; Kim, Hyungjoo; Park, Doosan; Bae, Sang Byung; Lee, Sungsoo; Lee, Moon Soo; Kim, Chang‐Jin; Baek, Moo Jun

doi:10.1186/1471-2407-14-164

Cited by 35 publications

(29 citation statements)

References 34 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CYR61 has been previously linked to tumor progression in PDAC, as well as several other tumor types including breast, gastric and colorectal cancers [49], [50], [51], [52], [53]. Moreover, prior work suggested that CYR61 expression is regulated by WNT/β-catenin signaling in hepatocellular carcinoma cells [54].…”

Section: Resultsmentioning

confidence: 99%

Activation of WNT/β-Catenin Signaling Enhances Pancreatic Cancer Development and the Malignant Potential Via Up-regulation of Cyr61

et al. 2016

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly develops following activating mutations in the KRAS oncogene. Activation of WNT signaling is also commonly observed in PDAC. To ascertain the impact of postnatal activation of WNT-stimulated signaling pathways in PDAC development, we combined the Elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-KrasG12D, Ptf1a-cre model. Delivery of RCAS viruses encoding β-cateninS37A and WNT1 stimulated the progression of premalignant pancreatic intraepithelial neoplasias (PanIN) and PDAC development. Moreover, mice injected with RCAS-β-cateninS37A or RCAS-Wnt1 had reduced survival relative to RCAS-GFP-injected controls (P < .05). Ectopic expression of active β-catenin, or its DNA-binding partner TCF4, enhanced transformation associated phenotypes in PDAC cells. In contrast, these phenotypes were significantly impaired by the introduction of ICAT, an inhibitor of the β-catenin/TCF4 interaction. By gene expression profiling, we identified Cyr61 as a target molecule of the WNT/β-catenin signaling pathway in pancreatic cancer cells. Nuclear β-catenin and CYR61 expression were predominantly detected in moderately to poorly differentiated murine and human PDAC. Indeed, nuclear β-catenin- and CYR61-positive PDAC patients demonstrated poor prognosis (P < .01). Knockdown of CYR61 in a β-catenin-activated pancreatic cancer cell line reduced soft agar, migration and invasion activity. Together, these data suggest that the WNT/β-catenin signaling pathway enhances pancreatic cancer development and malignancy in part via up-regulation of CYR61.

show abstract

Section: Resultsmentioning

confidence: 99%

Activation of WNT/β-Catenin Signaling Enhances Pancreatic Cancer Development and the Malignant Potential Via Up-regulation of Cyr61

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Cyr61 is a multifunctional protein involved in human CRC development and progression [23]. Overexpression of Cyr61 may induce the EMT, thereby leading to cancer cell invasion, metastasis, and poor prognosis [24,27].…”

Section: Discussionmentioning

confidence: 99%

“…Cyr61 is up regulated in many cancers, such as breast [19], esophagus [22], and colorectal cancers [23]. Several studies have reported that Cyr61 promotes the EMT and tumor metastasis [24,25].…”

Section: Introductionmentioning

confidence: 99%

Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer

Huang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Metastasis is the primary cause of colorectal cancer (CRC)-related death. However, the molecular mechanisms underlying metastasis in CRC remain unclear. Methods: We evaluated mRNA and protein expression levels by quantitative real-time reverse transcription PCR, western blotting, immunofluorescence, tissue microarrays, and immunohistochemistry assays. We also assessed the migration and invasion abilities of CRC cells in vitro by wound healing assays, invasion and migration assays, western blot analysis, and immunofluorescence. Tumor metastasis was evaluated in nude mice in vivo. Results: A positive correlation was observed between the expression patterns of Forkhead box k1 (FOXK1) and Snail in CRC. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that Snail directly bound to and activated the human FOXK1 gene promoter. Moreover, the Snail-FOXK1 axis promote epithelial mesenchymal transition (EMT)-mediated CRC cell invasion and metastasis. FOXK1 and Snail expression levels were correlated with tumor progression and served as significant predictors of overall survival in patients with CRC. Furthermore, overexpression of FOXK1 induced the EMT by upregulating the expression of cysteine-rich angiogenic inducer 61 (Cyr61). Luciferase assays showed that Cyr61 was a direct transcriptional target of FOXK1. Down regulation of Cyr61 decreased FOXK1-enhanced “CRC cell” migration, invasion, and metastasis. Additionally, FOXK1 expression was positively correlated with Cyr61 expression and was associated with poor prognosis. Conclusions: The Snail/FOXK1/Cyr61 signaling axis regulates the EMT and metastasis of CRC.

show abstract

“…Since CCN1 can be detected in cerebrospinal fluid it might serve as prognostic marker. Jeong et al (2014) examined CCN1 expression in six colorectal cell lines and 20 sets of paired normal and tumor tissues by western blot. 4/6 lines were higher in CCN1 and 16/ 20 tumor tissues.…”

Section: Ccn Proteins and Cancermentioning

confidence: 99%

CCN family of proteins: critical modulators of the tumor cell microenvironment

Yeger

Perbal

2016

J. Cell Commun. Signal.

View full text Add to dashboard Cite

The CCN family of proteins consisting of CCN1 (Cyr61), CCN2 (CTGF), CCN3 (NOV), CCN4 (WISP-1), CCN5 (WISP-2) and CCN6 (WISP-3) are considered matricellular proteins operating essentially in the extracellular microenvironment between cells. Evidence has also been gradually building since their first discovery of additional intracellular roles although the major activity is triggered at the cell membrane. The proteins consist of 4 motifs, a signal peptide (for secretion} followed consecutively by the IGFBP, VWC, TSP1 and CT (C-terminal cysteine knot domain) motifs, which signify their potential binding partners and functional connections to a variety of key regulators of physiological processes. With respect to cancer it is now clear that, whereas certain members can facilitate tumor behavior and progression, others can competitively counter the process. It is therefore clear that the net outcome of biological interactions in the matrix and what gets signaled or inhibited can be a function of the interplay of these CCN 1-6 proteins. Because the CCN proteins further interact with other key proteins, like growth factors in the matrix, the balance is not only important but can vary dynamically with the physiological states of tumor cells and the surrounding normal cells. The tumor niche with its many cell players has surfaced as a critical determinant of tumor behavior, invasiveness, and metastasis. It is in this context that CCN proteins should be investigated with the potential of being recognized and validated for future therapeutic approaches.

show abstract

Cyr61 Expression is associated with prognosis in patients with colorectal cancer

Cited by 35 publications

References 34 publications

Activation of WNT/β-Catenin Signaling Enhances Pancreatic Cancer Development and the Malignant Potential Via Up-regulation of Cyr61

Activation of WNT/β-Catenin Signaling Enhances Pancreatic Cancer Development and the Malignant Potential Via Up-regulation of Cyr61

Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer

CCN family of proteins: critical modulators of the tumor cell microenvironment

Contact Info

Product

Resources

About