ArticleThe Journal of biological chemistry2014
The adaptor proteins p66Shc and Grb2 regulate the activation of the GTPases ARF1 and ARF6 in invasive breast cancer cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
- Cytoskeletal dynamics in breast cancer: mechanistic insights and therapeutic opportunities.Journal of the National Cancer Center · 2026Review
- p66Shc Protein-Oxidative Stress Sensor or Redox Enzyme: Its Potential Role in Mitochondrial Metabolism of Human Breast Cancer.Cancers · 2024Article
- Relevance of the endoplasmic reticulum-mitochondria axis in cancer diagnosis and therapy.Experimental & molecular medicine · 2024Review
- The p66International journal of molecular sciences · 2023Review
- ARF6 promotes hepatocellular carcinoma proliferation through activating STAT3 signaling.Cancer cell international · 2023Article
- A circuit for secretion-coupled cellular autonomy in multicellular eukaryotic cells.Molecular systems biology · 2023Article
- Actin Modulation Regulates the Alpha-1-Syntrophin/p66Shc Mediated Redox Signaling Contributing to the RhoA GTPase Protein Activation in Breast Cancer Cells.Frontiers in oncology · 2022Article
- Ras, TrkB, and ShcA Protein Expression Patterns in Pediatric Brain Tumors.Journal of clinical medicine · 2021Article
- Identification of New Tumor-Related Gene Mutations in Chinese Gastrointestinal Stromal Tumors.Frontiers in cell and developmental biology · 2021Article
- GGA3-mediated recycling of the RET receptor tyrosine kinase contributes to cell migration and invasion.Oncogene · 2020Article
- Article
- p66ShcA functions as a contextual promoter of breast cancer metastasis.Breast cancer research : BCR · 2020Article
- Novel Insights Into Triple-Negative Breast Cancer Prognosis by Comprehensive Characterization of Aberrant Alternative Splicing.Frontiers in genetics · 2020Article
- KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma.Frontiers in genetics · 2020Article
- The p52 isoform of SHC1 is a key driver of breast cancer initiation.Breast cancer research : BCR · 2019Article
- The Germline Variants rs61757955 and rs34988193 Are Predictive of Survival in Lower Grade Glioma Patients.Molecular cancer research : MCR · 2019Article
- Adaptor Protein p66Shc: A Link Between Cytosolic and Mitochondrial Dysfunction in the Development of Diabetic Retinopathy.Antioxidants & redox signaling · 2019Article
- Histone deacetylase inhibitors suppress aggressiveness of head and neck squamous cell carcinoma via histone acetylation-independent blockade of the EGFR-Arf1 axis.Journal of experimental & clinical cancer research : CR · 2019Article
- Downregulation of TBC1 Domain Family Member 24 (BC1D24) Inhibits Breast Carcinoma Growth via IGF1R/PI3K/AKT Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Signals downstream of growth factor receptors play an important role in mammary carcinogenesis. Recently, we demonstrated that the small GTPases ARF1 and ARF6 were shown to be activated downstream of the epidermal growth factor receptor (EGFR) and act as a key regulator of growth, migration, and invasion of breast cancer cells. However, the mechanism via which the EGFR recruits and activates ARF1 and ARF6 to transmit signals has yet to be fully elucidated. Here, we identify adaptor proteins Grb2 and p66Shc as important regulators mediating ARF activation. We demonstrate that ARF1 can be found in complex with Grb2 and p66Shc upon EGF stimulation of the basal-like breast cancer MDA-MB-231 cell line. However, we report that these two adaptors regulate ARF1 activation differently, with Grb2 promoting ARF1 activation and p66Shc blocking this response. Furthermore, we show that Grb2 is essential for the recruitment of ARF1 to the EGFR, whereas p66Shc hindered ARF1 receptor recruitment. We demonstrate that the negative regulatory role of p66Shc stemmed from its ability to block the recruitment of Grb2/ARF1 to the EGFR. Conversely, p66Shc potentiates ARF6 activation as well as the recruitment of this ARF isoform to the EGFR. Interestingly, we demonstrate that Grb2 is also required for the activation and receptor recruitment of ARF6. Additionally, we show an important role for p66Shc in modulating ARF activation, cell growth, and migration in HER2-positive breast cancer cells. Together, our results highlight a central role for adaptor proteins p66Shc and Grb2 in the regulation of ARF1 and ARF6 activation in invasive breast cancer cells.
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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.