ArticleOncotarget2016
Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Helicobacter pylori infection activates the HIF-1α/ALS2/Rab5 signaling axis in gastric cells.Cell communication and signaling : CCS · 2026Article
- Rab5 nucleotide binding promotes oxidative metabolism to fuel hepatocellular carcinoma cell proliferation.The Journal of biological chemistry · 2026Article
- Function and regulation of Rab GTPases in cancers.Cell biology and toxicology · 2024Review
- Biological characterization of breast cancer spheroid formed by fast fabrication method.In vitro models · 2024Article
- Exosomes: a promising avenue for cancer diagnosis beyond treatment.Frontiers in cell and developmental biology · 2024Review
- Applications of Exosome Vesicles in Different Cancer Types as Biomarkers.Current molecular medicine · 2024Review
- Hypoxia-induced YAP activation and focal adhesion turnover to promote cell migration in mesenchymal TNBC cells.Cancer medicine · 2023Article
- HIF-1Journal of oncology · 2022Article
- His domain protein tyrosine phosphatase and Rabaptin-5 couple endo-lysosomal sorting of EGFR with endosomal maturation.Journal of cell science · 2021Article
- Hypoxia and Extracellular Acidification as Drivers of Melanoma Progression and Drug Resistance.Cells · 2021Review
- Endocytosis: a pivotal pathway for regulating metastasis.British journal of cancer · 2021Review
- Statins and endocrine resistance in breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Decreased inspired oxygen stimulates de novo formation of coronary collaterals in adult heart.Journal of molecular and cellular cardiology · 2021Article
- The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells.Scientific reports · 2020Article
- Inhibition of formyl peptide receptor 1 activity suppresses tumorigenicityAnnals of translational medicine · 2020Article
- Comprehensive Analysis of Expression, Clinicopathological Association and Potential Prognostic Significance of RABs in Pancreatic Cancer.International journal of molecular sciences · 2020Article
- Complex Rab4-Mediated Regulation of Endosomal Size and EGFR Activation.Molecular cancer research : MCR · 2020Article
- Rab GTPases: Emerging Oncogenes and Tumor Suppressive Regulators for the Editing of Survival Pathways in Cancer.Cancers · 2020Review
- Subversion of Ras Small GTPases in Cutaneous Melanoma Aggressiveness.Frontiers in cell and developmental biology · 2020Review
- Novel genetic variants ofAmerican journal of cancer research · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia, a common condition of the tumor microenvironment, is associated with poor patient prognosis, tumor cell migration, invasion and metastasis. Recent evidence suggests that hypoxia alters endosome dynamics in tumor cells, leading to augmented cell proliferation and migration and this is particularly relevant, because endosomal components have been shown to be deregulated in cancer. The early endosome protein Rab5 is a small GTPase that promotes integrin trafficking, focal adhesion turnover, Rac1 activation, tumor cell migration and invasion. However, the role of Rab5 and downstream events in hypoxia remain unknown. Here, we identify Rab5 as a critical player in hypoxia-driven tumor cell migration, invasion and metastasis. Exposure of A549 human lung carcinoma, ZR-75, MDA-MB-231 and MCF-7 human breast cancer and B16-F10 mouse melanoma cells to hypoxia increased Rab5 activation, followed by its re-localization to the leading edge and association with focal adhesions. Importantly, Rab5 was required for hypoxia-driven cell migration, FAK phosphorylation and Rac1 activation, as shown by shRNA-targeting and transfection assays with Rab5 mutants. Intriguingly, the effect of hypoxia on both Rab5 activity and migration was substantially higher in metastatic B16-F10 cells than in poorly invasive B16-F0 cells. Furthermore, exogenous expression of Rab5 in B16-F0 cells predisposed to hypoxia-induced migration, whereas expression of the inactive mutant Rab5/S34N prevented the migration of B16-F10 cells induced by hypoxia. Finally, using an in vivo syngenic C57BL/6 mouse model, Rab5 expression was shown to be required for hypoxia-induced metastasis. In summary, these findings identify Rab5 as a key mediator of hypoxia-induced tumor cell migration, invasion and metastasis.
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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.