ArticleOncogene2013
GAB2 induces tumor angiogenesis in NRAS-driven melanoma.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Exploring the importance of cancer pathways by meta-analysis of differential protein expression networks in three different cancers.Biology direct · 2016Pooled it
- Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3-year survival update and multi-omics analysis.Clinical and translational medicine · 2025Trial
- Article
- Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- New insights into RAS in head and neck cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Hypoxia in Skin Cancer: Molecular Basis and Clinical Implications.International journal of molecular sciences · 2023Review
- Article
- Cutaneous Melanoma: Mutational Status and Potential Links to Tertiary Lymphoid Structure Formation.Frontiers in immunology · 2021Review
- MicroRNA‑218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2.Oncology reports · 2020Article
- Synergistic effects of SHP2 and PI3K pathway inhibitors in GAB2-overexpressing ovarian cancer.American journal of cancer research · 2019Article
- Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Elevated Gab2 induces tumor growth and angiogenesis in colorectal cancer through upregulating VEGF levels.Journal of experimental & clinical cancer research : CR · 2017Article
- Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression.Oncogene · 2016Article
- Standard melanoma-associated markers do not identify the MM127 metastatic melanoma cell line.Scientific reports · 2016Article
- Review
- Structure and function of Gab2 and its role in cancer (Review).Molecular medicine reports · 2015Review
- Hypoxia-independent drivers of melanoma angiogenesis.Frontiers in oncology · 2015Review
- GAB2--a scaffolding protein in cancer.Molecular cancer research : MCR · 2012Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
GAB2 is a scaffold protein with diverse upstream and downstream effectors. MAPK and PI3K signaling pathways are known effectors of GAB2. It is amplified and overexpressed in a variety of human tumors including melanoma. Here we show a previously undescribed role for GAB2 in NRAS-driven melanoma. Specifically, we found that GAB2 is co-expressed with mutant NRAS in melanoma cell lines and tumor samples and its expression correlated with metastatic potential. Co-expression of GAB2(WT) and NRAS(G12D) in melanocytes and in melanoma cells increased anchorage-independent growth by providing GAB2-expressing cells a survival advantage through upregulation of BCL-2 family of anti-apoptotic factors. Of note, collaboration of GAB2 with mutant NRAS enhanced tumorigenesis in vivo and led to an increased vessel density with strong CD34 and VEGFR2 activity. We found that GAB2 facilitiated an angiogenic switch by upregulating HIF-1α and VEGF levels. This angiogenic response was significantly suppressed with the MEK inhibitor PD325901. These data suggest that GAB2-mediated signaling cascades collaborate with NRAS-driven downstream activation for conferring an aggressive phenotype in melanoma. Second, we show that GAB2/NRAS signaling axis is non-linear and non-redundant in melanocytes and melanoma, and thus are acting independent of each other. Finally, we establish a link between GAB2 and angiogenesis in melanoma for the first time. In conclusion, our findings provide evidence that GAB2 is a novel regulator of tumor angiogenesis in NRAS-driven melanoma through regulation of HIF-1α and VEGF expressions mediated by RAS-RAF-MEK-ERK signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.