ArticleCancer research2021
Epigenetic and Posttranscriptional Modulation of SOS1 Can Promote Breast Cancer Metastasis through Obesity-Activated c-Met Signaling in African-American Women.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Penetrative biomimetic nanovehicle boosts immunotherapy in triple-negative breast cancer via SOS1 blockade.Asian journal of pharmaceutical sciences · 2025Article
- HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3-containing extracellular vesicles.The Journal of clinical investigation · 2025Article
- PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells.Discover oncology · 2025Article
- Article
- Emerging Roles of PTTG1/Securin in Breast Cancer.Journal of Cancer · 2025Review
- Prognostic value of c-MET in oesophageal squamous cell carcinoma: a study based on the mRNA expression in TCGA database and a meta-analysis.Frontiers in medicine · 2025Article
- Imperative role of adaptor proteins in macrophage toll-like receptor signaling pathways.Future science OA · 2024Review
- Obesity and Early-Onset Breast Cancer and Specific Molecular Subtype Diagnosis in Black and White Women: NIMHD Social Epigenomics Program.JAMA network open · 2024Article
- Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.Molecular cancer · 2024Review
- The interrelationship between obesity and race in breast cancer prognosis: a prospective cohort study.BMC women's health · 2024Article
- DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal and tumor growth of cancer stem-like cells derived from non-small cell lung cancer.Clinical epigenetics · 2024Article
- Racial Disparities in Breast Cancer Treatments and Adverse Events in the SEER-Medicare Data.Cancers · 2023Article
- EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression.Cell death & disease · 2023Article
- The Adipocyte-Macrophage Relationship in Cancer: A Potential Target for Antioxidant Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- An insight into novel therapeutic potentials of taxifolin.Frontiers in pharmacology · 2023Review
- Exosomal miR-1304-3p promotes breast cancer progression in African Americans by activating cancer-associated adipocytes.Nature communications · 2022Article
- The structural basis of BCR-ABL recruitment of GRB2 in chronic myelogenous leukemia.Biophysical journal · 2022Article
- MicroRNAs and Cancer Racial Disparities.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Ethnicity is considered to be one of the major risk factors in certain subtypes of breast cancer. However, the mechanism of this racial disparity remains poorly understood. Here, we demonstrate that SOS1, a key regulator of Ras pathway, is highly expressed in African-American (AA) patients with breast cancer compared with Caucasian-American patients. Because of the higher obesity rate in AA women, increased levels of SOS1 facilitated signal transduction of the c-Met pathway, which was highly activated in AA patients with breast cancer via hepatocyte growth factor secreted from adipocytes. Elevated expression of SOS1 also enhanced cancer stemness through upregulation of PTTG1 and promoted M2 polarization of macrophages by CCL2 in metastatic sites. SOS1 was epigenetically regulated by a super-enhancer identified by H3K27ac in AA patients. Knockout of the super-enhancer by CRISPR in AA cell lines significantly reduced SOS1 expression. Furthermore, SOS1 was posttranscriptionally regulated by miR-483 whose expression is reduced in AA patients through histone trimethylation (H3K27me3) on its promoter. The natural compound, taxifolin, suppressed signaling transduction of SOS1 by blocking the interaction between SOS1 and Grb2, suggesting a potential utility of this compound as a therapeutic agent for AA patients with breast cancer. SIGNIFICANCE: These findings elucidate the signaling network of SOS1-mediated metastasis in African-American patients, from the epigenetic upregulation of SOS1 to the identification of taxifolin as a potential therapeutic strategy against SOS1-driven tumor progression.
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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.