ArticleThe Journal of cell biology2013
Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia.
Article in The Journal of cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review.Molecular cancer · 2019Pooled it
- Cancer-associated adipomes promote invadopodia formation and enhance metastatic potential in triple-negative breast cancer.NPJ breast cancer · 2026Article
- Immune Checkpoint Blockade and Emerging Combination Platforms in Breast Cancer: A Narrative Review.Breast cancer (Dove Medical Press) · 2026Review
- The Multiple Functions of HB-EGF in Female Reproduction and Related Cancer: Molecular Mechanisms and Targeting Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Unveiling miRNA30b's Role in Suppressing ADAM12 to Combat Triple-Negative Breast Cancer.The breast journal · 2024Article
- Evaluating the Role of Methylated Circulating Tumor DNA in Combination With Pathological Prognostic Factors for Predicting Recurrence of Colorectal Cancer.Biomarker insights · 2024Article
- Invasion-Block and S-MARVEL: A high-content screening and image analysis platform identifies ATM kinase as a modulator of melanoma invasion and metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Expression of stem cell markers SALL4, LIN28A, and KLF4 in ameloblastoma.Diagnostic pathology · 2023Article
- Inferring ligand-receptor cellular networks from bulk and spatial transcriptomic datasets with BulkSignalR.Nucleic acids research · 2023Article
- The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights.Cancers · 2023Review
- ADAM12 abrogation alters immune cell infiltration and improves response to checkpoint blockade therapy in the T11 murine model of triple-negative breast cancer.Oncoimmunology · 2023Article
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Proteolytic and mechanical remodeling of the extracellular matrix by invadopodia in cancer.Physical biology · 2022Review
- Hydroxylation of the NOTCH1 intracellular domain regulates Notch signaling dynamics.Cell death & disease · 2022Article
- Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes.American journal of human genetics · 2022Article
- Elevation of ADAM12 facilitates tumor progression by enhancing metastasis and immune infiltration in gastric cancer.International journal of oncology · 2022Article
- Heat Shock Proteins 70 Regulate Cell Motility and Invadopodia-Associated Proteins Expression in Oral Squamous Cell Carcinoma.Frontiers in endocrinology · 2022Article
- Review
- Hypoxia-inducible factor-dependent ADAM12 expression mediates breast cancer invasion and metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Key proteins of invadopodia are overexpressed in oral squamous cell carcinoma suggesting an important role of MT1-MMP in the tumoral progression.Diagnostic pathology · 2021Observational
29 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Notch regulates cell-cell contact-dependent signaling and is activated by hypoxia, a microenvironmental condition that promotes cellular invasion during both normal physiology and disease. The mechanisms by which hypoxia and Notch regulate cellular invasion are not fully elucidated. In this paper, we show that, in cancer cells, hypoxia increased the levels and activity of the ADAM12 metalloprotease in a Notch signaling-dependent manner, leading to increased ectodomain shedding of the epidermal growth factor (EGF) receptor (EGFR) ligand heparin-binding EGF-like growth factor. Released HB-EGF induced the formation of invadopodia, cellular structures that aid cancer cell invasion. Thus, we describe a signaling pathway that couples cell contact-dependent signaling with the paracrine activation of the EGFR, indicating cross talk between the Notch and EGFR pathways in promoting cancer cell invasion. This signaling pathway might regulate the coordinated acquisition of invasiveness by neighboring cells and mediate the communication between normoxic and hypoxic areas of tumors to facilitate cancer cell invasion.
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Registered trials
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