Cyr61/CCN1 is a tumor suppressor in human hepatocellular carcinoma and involved in DNA damage response
Abstract
Cyr61/CCN1 is a secreted extracellular matrix associated protein involved in diverse biological functions and plays multiple roles in tumorigenesis. Cyr61 was down-regulated in HCC tumor tissues as observed in our previous cDNA microarray study, but its potential role in hepatocarcinogenesis is still unclear. To explore the biological significance of Cyr61 in HCC development, over-expression of this gene was established in HCC cell lines and its effects on cell proliferation, adhesion, migration and invasion were analyzed in this study. Cyr61 expression was down-regulated in HCC tumors as measured by quantitative real-time PCR and its protein level was decreased in most HCC cell lines as detected by Western blot. Over-expression of Cyr61 in HCC cell lines suppressed cell proliferation in monolayer and anchorage-independent growth in soft agar, whereas down-regulation of Cyr61 by siRNA increased cell proliferation rate. Over-expression of Cyr61 also significantly enhanced adhesion activities of HepG2 cells to various ECM proteins. Moreover, stably transfected HepG2-Cyr61 cells showed inhibited cell mobility (40-45%) and reduced invasiveness (30-40%) compared to HepG2-Neo controls. Furthermore, upon exposure to 5-Fluorouracil and UV irradiation, Cyr61 was rapidly induced in both p53(+/+) HepG2 and p53(-/-) Hep3B cells. However, only HepG2 cells showed increased G2/M phase arrest with concomitant up-regulation in p53 and p21 levels, suggesting that Cyr61 may play an active role in regulating HCC cell growth involving p53 as well as alternative pathways. In conclusion, we demonstrated that Cyr61 is a tumor suppressor in hepatocarcinogenesis and is involved in DNA damage response.
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Overexpression of CCN1 inhibits proliferation of hepatocellular carcinoma cells, in part through p53.
“Likewise, overexpression of CCN1 inhibits the proliferation of hepatocellular carcinoma cells, in part through p53 [159].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [159]
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- Authors
- Feng, P., Wang, B., & Ren, E. C.
- Affiliations
- Genome Institute of Singapore (SG)
- National University of Singapore (SG)
- Corresponding author
- Ren, Ee Chee
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2008
- Volume
- 40
- Issue
- 1
- Pages
- 98-109
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2030801731
- Cited by
- 51
- References
- 42
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 1 · 2012: 7
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Funders
- National University of Singapore
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- hepatocellular carcinoma, tumor suppressor, DNA damage response, p53, p21, extracellular matrix, cell proliferation, cell migration and invasion, anchorage-independent growth, G2/M cell cycle arrest, hepatocarcinogenesis, 5-fluorouracil, UV irradiation
- MeSH terms
- Cell Movement, DNA Damage, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Neoplasm Invasiveness, SOS Response, Genetics, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Gene Transfer Techniques, RNA, Small Interfering, Cell Line, Tumor, Cell Proliferation, Cell Migration Assays, Cysteine-Rich Protein 61
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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