ArticleOncogene2015
An EGFR/PI3K/AKT axis promotes accumulation of the Rac1-GEF Tiam1 that is critical in EGFR-driven tumorigenesis.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
- The Role of KRAS in Non-Small Cell Lung Cancer: From Molecular Background to Precision Medicine.International journal of molecular sciences · 2026Review
- ARHGEF7 S-glutathionylation promotes cancer cell migration through Rac1 activation.bioRxiv : the preprint server for biology · 2026Article
- Inhibitors of De Novo Guanylate Biosynthesis Enhance the Potency of MAPK Cascade Inhibitors Against Colorectal Cancer.International journal of molecular sciences · 2025Article
- The LCLAT1/LYCAT acyltransferase is required for EGF-mediated phosphatidylinositol-3,4,5-trisphosphate generation and Akt signaling.Molecular biology of the cell · 2024Article
- The Roles of RAC1 and RAC1B in Colorectal Cancer and Their Potential Contribution to Cetuximab Resistance.Cancers · 2024Review
- Guanine nucleotide exchange factors and colon neoplasia.Frontiers in cell and developmental biology · 2024Review
- Nectin-4 regulates cellular senescence-associated enlargement of cell size.Scientific reports · 2023Article
- A TIAM1-TRIM28 complex mediates epigenetic silencing of protocadherins to promote migration of lung cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.Circulation research · 2023Article
- A20 interacts with mTORC2 to inhibit the mTORC2/Akt/Rac1 signaling axis in hepatocellular carcinoma cells.Cancer gene therapy · 2023Article
- T-box transcription factor 19 promotes hepatocellular carcinoma metastasis through upregulating EGFR and RAC1.Oncogene · 2022Article
- Hypoxia-induced Fascin-1 upregulation is regulated by Akt/Rac1 axis and enhances malignant properties of liver cancer cells via mediating actin cytoskeleton rearrangement and Hippo/YAP activation.Cell death discovery · 2021Article
- The 14-3-3η/GSK-3β/β-catenin complex regulates EndMT induced by 27-hydroxycholesterol in HUVECs and promotes the migration of breast cancer cells.Cell biology and toxicology · 2021Article
- RAC1B modulates intestinal tumourigenesis via modulation of WNT and EGFR signalling pathways.Nature communications · 2021Article
- Role of the V1G1 subunit of V-ATPase in breast cancer cell migration.Scientific reports · 2021Article
- Involvement of miR-619-5p in resistance to cisplatin by regulating ATXN3 in oral squamous cell carcinoma.International journal of biological sciences · 2021Article
- Review
- Article
- Differential Subcellular Distribution and Translocation of Seven 14-3-3 Isoforms in Response to EGF and During the Cell Cycle.International journal of molecular sciences · 2020Article
- PODXL2 maintains cellular stemness and promotes breast cancer development through the Rac1/Akt pathway.International journal of medical sciences · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor receptor (EGFR) signaling regulates cell growth and survival, and its overactivation drives cancer development. One important branch of EGFR signaling is through activation of GTPase Rac1, which further promotes cell proliferation, survival and cancer metastasis. Here, we show that EGFR activates Rac1 via inducing the accumulation of its specific guanine nucleotide exchange factor, T-cell lymphoma invasion and metastasis 1 (Tiam1) in non-small-cell lung cancer and colon cancer cells. Conversely, elevated Tiam1 is required for EGFR-induced tumorigenesis. In human lung adenocarcinoma and colon cancer specimens, Tiam1 expression strongly correlates with EGFR expression. We further reveal that AKT, a key downstream protein kinase of EGFR, phosphorylates Tiam1 at several consensus sites, facilitates the interaction of Tiam1 with scaffold proteins 14-3-3 and leads to an increase of Tiam1 stability. Subsequently, Tiam1 is dephosporylated and destabilized by PP2A. Together, our study identifies a bidirectional (phosphorylation and dephosphorylation) regulatory mechanism controlling Tiam1 stability and provides new insights on how EGFR signaling triggers Rac1 activation and cancer development.
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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.