ArticleCancer science2014
Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.
Article in Cancer science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- ANGPTL2 inhibits macrophage pyroptosis and alleviates rheumatoid arthritis progression by regulating mitophagy via IGFBP5.Cell death & disease · 2026Article
- Context-Dependent Roles of ANGPTL2-Mediated Inflammaging in Tissue Homeostasis, Pathological Tissue Remodeling, and Longevity.Aging cell · 2026Article
- The Two Faces of Angiopoietin-Like Protein 2 in Cancer.Cancer science · 2025Review
- Host ANGPTL2 establishes an immunosuppressive tumor microenvironment and resistance to immune checkpoint therapy.Cancer science · 2024Article
- Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer.Biochemical and biophysical research communications · 2024Review
- Angiopoietin-Like Protein 2 Expression in Tumor Cells Supports Tumor-Associated Macrophage-Induced Tumor Progression in Esophageal Cancer.Annals of surgical oncology · 2024Article
- Comparative transcriptomic analysis validates iPSC derived in-vitro progressive fibrosis model as a screening tool for drug discovery and development in systemic sclerosis.Scientific reports · 2024Article
- Tumor stroma-derived ANGPTL2 potentiates immune checkpoint inhibitor efficacy.Cancer gene therapy · 2024Article
- ANGPTL2-mediated epigenetic repression of MHC-I in tumor cells accelerates tumor immune evasion.Molecular oncology · 2023Article
- Angptl2 is a Marker of Cellular Senescence: The Physiological and Pathophysiological Impact of Angptl2-Related Senescence.International journal of molecular sciences · 2021Review
- Angiopoietin-like Proteins in Colorectal Cancer-A Literature Review.International journal of molecular sciences · 2021Review
- Relationship between miR-204 and ANGPTL2 expression and diagnosis, pathological stage, and prognosis in patients with colon cancer.Translational cancer research · 2021Article
- Stroma-derived ANGPTL2 establishes an anti-tumor microenvironment during intestinal tumorigenesis.Oncogene · 2021Article
- Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity.Genes & development · 2019Article
- Article
- Angiopoietin-Like Proteins in Angiogenesis, Inflammation and Cancer.International journal of molecular sciences · 2018Review
- Balancing signals in the intestinal niche.The EMBO journal · 2017Article
- ANGPTL2 expression in the intestinal stem cell niche controls epithelial regeneration and homeostasis.The EMBO journal · 2017Article
- High Circulating Levels of ANGPTL2: Beyond a Clinical Marker of Systemic Inflammation.Oxidative medicine and cellular longevity · 2017Review
- Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiopoietin-like protein 2 (ANGPTL2) plays an important role in inflammatory carcinogenesis and tumor metastasis by activating tumor angiogenesis and tumor cell chemotaxis and invasiveness. However, it is unclear whether ANGPTL2 expression has an effect on tumor cell survival. Here, we explored that possibility by determining whether ANGPTL2 expression altered survival of human colorectal cancer cell lines treated with antineoplastic drugs. To do so, we generated SW480 cells expressing ANGPTL2 (SW480/ANGPTL2) and control (SW480/Ctrl) cells. Apoptosis induced by antineoplastic drug treatment was significantly decreased in SW480/ANGPTL2 compared to control cells. Expression of anti-apoptotic BCL-2 family genes was upregulated in SW480/ANGPTL2 compared to SW480/Ctrl cells. To assess signaling downstream of ANGPTL2 underlying this effect, we carried out RNA sequencing analysis of SW480/ANGPTL2 and SW480/Ctrl cells. That analysis, combined with in vitro experiments, indicated that Syk-PI3K signaling induced expression of BCL-2 family genes in SW480/ANGPTL2 cells. Furthermore, ANGPTL2 increased its own expression in a feedback loop by activating the spleen tyrosine kinase-nuclear factor of activated T cells (Syk-NFAT) pathway. Finally, we observed a correlation between higher ANGPTL2 expression in primary unresectable tumors from colorectal cancer patients who underwent chemotherapy with a lower objective response rate. These findings suggest that attenuating ANGPTL2 signaling in tumor cells may block tumor cell resistance to antineoplastic therapies.
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