ArticleOncotarget2015
Hypoxia/reoxygenation-experienced cancer cell migration and metastasis are regulated by Rap1- and Rac1-GTPase activation via the expression of thymosin beta-4.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Mechanisms of Cell Fusion in Cancer.Results and problems in cell differentiation · 2024Review
- Expression Status of Rap1 Pathway-Related Genes in Liver Metastases Compared with Corresponding Primary Colorectal Cancer.Cancers · 2023Article
- Single-Cell Analysis of Unidirectional Migration of Glioblastoma Cells Using a Fiber-Based Scaffold.ACS applied bio materials · 2023Article
- Identification of phenotype-specific networks from paired gene expression-cell shape imaging data.Genome research · 2022Article
- Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line.Journal of personalized medicine · 2021Article
- Di-(2-ethylhexyl) phthalate-induced tumor growth is regulated by primary cilium formation via the axis of HInternational journal of medical sciences · 2021Article
- Effects of hub genes on the clinicopathological and prognostic features of lung adenocarcinoma.Oncology letters · 2020Article
- Targeting Rac and Cdc42 GEFs in Metastatic Cancer.Frontiers in cell and developmental biology · 2020Review
- Tumor-derived exosomal miRNA-320d as a biomarker for metastatic colorectal cancer.Journal of clinical laboratory analysis · 2019Article
- Curcumin-Induced Autophagy Augments Its Antitumor Effect against A172 Human Glioblastoma Cells.Biomolecules & therapeutics · 2019Article
- Thymosin β-4 is a novel regulator for primary cilium formation by nephronophthisis 3 in HeLa human cervical cancer cells.Scientific reports · 2019Article
- Hypoxia and HIF activation as a possible link between sepsis and thrombosis.Thrombosis journal · 2019Article
- Pathway-based dissection of the genomic heterogeneity of cancer hallmarks' acquisition with SLAPenrich.Scientific reports · 2018Article
- Silencing Ras-Related C3 Botulinum Toxin Substrate 1 Inhibits Growth and Migration of Hypopharyngeal Squamous Cell Carcinoma via the P38 Mitogen-Activated Protein Kinase Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Increased Expression of Thymosin βJournal of pathology and translational medicine · 2017Article
- Cancer Cell Fusion: Mechanisms Slowly Unravel.International journal of molecular sciences · 2016Review
- TIPE2 suppresses angiogenesis and non-small cell lung cancer (NSCLC) invasiveness via inhibiting Rac1 activation and VEGF expression.Oncotarget · 2016Article
- Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis.Oncotarget · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling by small guanosine triphosphatases (GTPase), Rap1/Rac1, is one of the major pathways controlling cancer cell migration and tumor metastasis. Thymosin beta-4 (Tβ4), an actin-sequestering protein, has been shown to increase migration of cancer cells. Episodes of hypoxia and re-oxygenation (H/R) are an important phenomenon in tumor microenvironment (TME). We investigated whether Tβ4 could play as an intermediary to crosstalk between Rac1- and Rap1- GTPase activation under hypoxia/reoxygenation (H/R) conditions. Inhibition of Tβ4 expression using transcription activator-like effector nucleases (TALEN) significantly decreased lung metastasis of B16F10 cells. Rac1 and Rap1 activity, as well as cancer cell migration, increased following induction of Tβ4 expression in normoxia- or H/R-experienced cells, but were barely detectable in Tβ4-depleted cells. Rap1-regulated Rac1 activity was decreased by a dominant negative Rap1 (Rap1N17), and increased by 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (CPT), a Rap1 activator. In contrast, a Rac1-specific inhibitor, NSC23766, and dominant negative Rac1 (Rac1N17) enhanced Tβ4 expression and aberrant Rap1 activity. While NSC23766 and Rac1N17 incompletely inhibited tumor metastasis in vivo, and H/R-experienced cancer cell migration in vitro, more efficient attenuation of cancer cell migration was accomplished by simultaneous inactivation of Rap1 and Rac1 with Rap1N17 and Rac1N17, respectively. These data suggest that a combination therapy targeting both Rap1 and Rac1 activity may be an effective method of inhibiting tumor metastasis.
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