Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway
Open accessAbstract
Tumor angiogenesis is essential for tumor growth and metastasis and is dependent on key angiogenic factors. Angiogenin (ANG), a 14.2-kDa polypeptide member of the RNase A superfamily, is an angiogenic protein that has been reported to be upregulated and associated with poor prognosis in some human cancers. The mechanisms through which aberrant ANG levels promote specific steps in tumor progression are unknown. Here, we show that ANG expression in human tissues is strongly correlated with an invasive cancer phenotype. We also show that ANG induces cellular survival, proliferation, endothelial tube formation and xenograft angiogenesis and growth. Novel mechanistic investigations revealed that ANG expression stimulated matrix metallopeptidase-2 (MMP2) expression through the phosphorylation of ERK1/2. Targeting ANG in vivo with N65828, a small-molecule inhibitor of the ribonucleolytic activity of human ANG, resulted in the diminution of xenograft tumoral growth through the inhibition of angiogenesis. Our findings support an unrecognized interplay between ANG, ERK1/2 and MMP2 that can impact tumor growth and progression. The targeting of ANG and associated factors could provide a novel strategy to inhibit tumor establishment and growth.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
S. epidermidis association promotes expression of angiogenesis genes Ang and Hgf and tissue repair genes Ceacam1, Grn, Hmox1, Igf1, and Pdgfa.
“S. epidermidis association promoted the expression of genes associated specifically with angiogenesis, including angiogenin (Ang) and Hgf (47, 48), as well as genes that more broadly promote tissue repair, like Ceacam1, Grn, Hmox1, Igf1, and Pdgfa (49–53) (Fig. 3R).”
From MAIT cells are imprinted by the microbiota in early life and promote tissue repair (2019) · cites this paper as [48]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 47 · Cited by 103
- Authors
- Miyake, M., Goodison, S., Lawton, A., Gomes-Giacoia, E., & Rosser, C. J.
- Affiliations
- Orlando Health (US)
- Nonagen Bioscience (United States) (US)
- Corresponding author
- Rosser, C J
- ORCID
- Venue
- Oncogene
- Published
- 2014-02-24
- Volume
- 34
- Issue
- 7
- Pages
- 890-901
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC4317372
- OpenAlex
- W2008304553
- Cited by
- 103
- References
- 47
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 8 · 2023: 5 · 2022: 11 · 2021: 7 · 2020: 7 · 2019: 13 · 2018: 11 · 2017: 9 · 2016: 7 · 2015: 8 · 2014: 2
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA116161)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- angiogenin, tumor angiogenesis, tumor growth, ERK signaling, ERK1/2 phosphorylation, ribonuclease inhibition, endothelial tube formation, tumor invasion, tumor xenografts, cancer therapy targets
- MeSH terms
- Animals, Humans, Mice, Inbred BALB C, Mice, Nude, Neoplasm Metastasis, Neoplasm Proteins, Neoplasm Transplantation, Neoplasms, Neovascularization, Pathologic, Ribonuclease, Pancreatic, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Mitogen-Activated Protein Kinase 1, Matrix Metalloproteinase 2, MAP Kinase Signaling System, Cell Line, Tumor, Mitogen-Activated Protein Kinase 3, Mice, Heterografts
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 ›
Are you an author, or do you see a problem with this page? Request a review
