ArticleJournal of translational medicine2023
BRAF D594A mutation defines a unique biological and immuno-modulatory subgroup associated with functional CD8
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 3 citations in OpenAlex.
- Loss of GGT6 promotes colorectal cancer progression and correlates with poor prognosis: a study based on multi-database mining and functional validation.Translational cancer research · 2026Article
- Mechanisms of immune resistance in microsatellite-stable colorectal cancer.Frontiers in oncology · 2026Review
- Prdm12 governs an epigenetic checkpoint linking neuroimmune cross-talk to CD8Science advances · 2025Article
- Accurate Transcription Factor Activity Inference to Decipher Cell Identity from Single-Cell Transcriptomic Data with MetaTF.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBRAF non-V600 mutation occupies a relatively small but critical subset in colorectal cancer (CRC). However, little is known about the biological functions and impacts of BRAF class III mutation in CRC. Here, we aim to explore how D594A mutation impacts on biological behaviors and immune related signatures in murine CRC cells.
methodsBRAF V600E (class I), G469V (class II) and D594A (class III) mutant cell lines were established based on MC38 cells. The biological behaviors of cells were evaluated in respect of cell growth, cell proliferation, cell apoptosis, cell migration and invasion by the methods of colony-forming assay, CCK-8 assay, Annexin V/PI staining and transwell assay. The concentrations of soluble cytokines were detected by ELISA. The membrane expression of immuno-modulatory molecules and the pattern of tumor infiltrating lymphocyte were evaluated by flow cytometry. The molecular mechanism was explored by RNA sequencing. Immunohistochemistry (IHC) staining was used for the detection of CD8α in tumor tissues. qRT-PCR and western blot were performed to assess the mRNA and protein expression. Anti-PD-L1 treatment and cytokines neutralization experiments were conducted in in vivo models.
resultsD594A mutant cells displayed lower grade malignancy characteristics than V600E (class I) and G469V (class II) mutant cells. Meanwhile, D594A mutation led to evident immuno-modulatory features including upregulation of MHC Class I and PD-L1. In vivo experiments displayed that the frequency of infiltrated CD8
conclusionsD594A mutant CRC exhibited lower aggressiveness and immune-activated phenotype. ATF3-THBS1-CXCL9/CXCL10 axis mediated functional CD8
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