ArticleCellular signalling2018
Oncogenic RAC1 and NRAS drive resistance to endoplasmic reticulum stress through MEK/ERK signalling.
Article in Cellular signalling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Sex-Specific Proteomic Profiling Identifies Pregnancy Zone Protein as a Complement-Linked Marker of Adverse Prognosis in Esophageal Adenocarcinoma.International journal of cancer · 2026Article
- The Role of Cysteine-Rich Protein 2 in Aortic Dissection: Implications for VSMC Phenotypic Modulation-CSRP2 Impedes the Progression of Aortic Dissection.Biomolecules · 2026Article
- Oxidative stress and endoplasmic reticulum stress in acute kidney injury: mechanistic crosstalk and therapeutic modulation.Frontiers in medicine · 2026Review
- Investigating the molecular mechanisms of phytochemicals targeting Ras-related C3 botulinum toxin substrate 1 (Rac1) to inhibit breast cancer metastasis via endoplasmic reticulum stress and Wnt-PCP signaling pathway.Journal of molecular modeling · 2025Article
- Effects of NaCell biochemistry and biophysics · 2025Review
- The Hsa_circ_0105558/miR-182-5p/ATF6 Cascade Affects HBiochemical genetics · 2025Article
- Acute kidney injury: exploring endoplasmic reticulum stress-mediated cell death.Frontiers in pharmacology · 2024Review
- MAPK Inhibition Requires Active RAC1 Signaling to Effectively Improve Iodide Uptake by Thyroid Follicular Cells.Cancers · 2021Article
- Endoplasmic Reticulum Stress Induces CAP2 Expression Promoting Epithelial-Mesenchymal Transition in Liver Cancer Cells.Molecules and cells · 2021Article
- Rac1, A Potential Target for Tumor Therapy.Frontiers in oncology · 2021Review
- Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency.International journal of molecular sciences · 2020Article
- RAC1mutation is not a predictive biomarker for PI3'-kinase-β-selective pathway-targeted therapy.Pigment cell & melanoma research · 2020Article
- TNFAIP8 promotes AML chemoresistance by activating ERK signaling pathway through interaction with Rac1.Journal of experimental & clinical cancer research : CR · 2020Article
- Review
- Splice switching an oncogenic ratio of SmgGDS isoforms as a strategy to diminish malignancy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress.Frontiers in cell and developmental biology · 2020Article
- CSRP2 suppresses colorectal cancer progressionTheranostics · 2020Article
- Article
- RAC1 Takes the Lead in Solid Tumors.Cells · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cancer cells are able to survive under conditions that cause endoplasmic reticulum stress (ER-stress), and can adapt to this stress by upregulating cell-survival signalling pathways and down-regulating apoptotic pathways. The cellular response to ER-stress is controlled by the unfolded protein response (UPR). Small Rho family GTPases are linked to many cell responses including cell growth and apoptosis. In this study, we investigate the function of small GTPases in cell survival under ER-stress. Using siRNA screening we identify that RAC1 promotes cell survival under ER-stress in cells with an oncogenic N92I RAC1 mutation. We uncover a novel connection between the UPR and N92I RAC1, whereby RAC1 attenuates phosphorylation of EIF2S1 under ER-stress and drives over-expression of ATF4 in basal conditions. Interestingly, the UPR connection does not drive resistance to ER-stress, as knockdown of ATF4 did not affect this. We further investigate cancer-associated kinase signalling pathways and show that RAC1 knockdown reduces the activity of AKT and ERK, and using a panel of clinically important kinase inhibitors, we uncover a role for MEK/ERK, but not AKT, in cell viability under ER-stress. A known major activator of ERK phosphorylation in cancer is oncogenic NRAS and we show that knockdown of NRAS in cells, which bear a Q61 NRAS mutation, sensitises to ER-stress. These findings highlight a novel mechanism for resistance to ER-stress through oncogenic activation of MEK/ERK signalling by small GTPases.
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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.