ArticleMolecular cancer2017
Secretory RAB GTPase 3C modulates IL6-STAT3 pathway to promote colon cancer metastasis and is associated with poor prognosis.
Article in Molecular cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 81 citations in OpenAlex.
- Construction of the survival nomograms for colon cancer patients of different ages based on the SEER database.Journal of cancer research and clinical oncology · 2023Trial
- Cancer Stem Cells in Colorectal Cancer: From Molecular Mechanisms to Diagnosis, Prognosis and Therapy Implications.Cancers · 2026Review
- Prognostic prediction nomogram of elderly patients with metastasis colon cancer and distant metastasis pattern: a SEER database analysis.Translational cancer research · 2025Article
- Comprehensive characterization of lysosome-dependent cell death reveals prognostic significance and immune landscape in colon adenocarcinoma.Scientific reports · 2025Article
- Rhaponticin inhibits the proliferation, migration, and invasion of head and neck squamous cell carcinoma (HNSCC) cells through modulation of the IL6/STAT3 signaling pathway.Discover oncology · 2025Article
- RAB3B Dictates mTORC1/S6 Signaling in Chordoma and Predicts Response to mTORC1-Targeted Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Rab3B Proteins: Cellular Functions, Regulatory Mechanisms, and Potential as a Cancer Therapy Target.Cell biochemistry and biophysics · 2025Review
- Systematic gene expression analysis of putative target genes linked to miR-31 in 83 oral squamous cell carcinoma samples.Head & face medicine · 2025Article
- Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety.Nature metabolism · 2024Article
- Article
- Function and regulation of Rab GTPases in cancers.Cell biology and toxicology · 2024Review
- RAB31 drives extracellular vesicle fusion and cancer-associated fibroblast formation leading to oxaliplatin resistance in colorectal cancer.Journal of extracellular biology · 2024Article
- The Role of Rab GTPases in the development of genetic and malignant diseases.Molecular and cellular biochemistry · 2024Review
- Aberrant methylation in neurofunctional gene serves as a hallmark of tumorigenesis and progression in colorectal cancer.BMC cancer · 2023Article
- Comparative transcriptome analysis of endothelial progenitor cells of HbSS patients with and without proliferative retinopathy.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Overexpression of synaptic vesicle protein Rab GTPase 3C promotes vesicular exocytosis and drug resistance in colorectal cancer cells.Molecular oncology · 2023Article
- Insights of Endocytosis Signaling in Health and Disease.International journal of molecular sciences · 2023Review
- Identification of Immune-Related Genes as Biomarkers for Uremia.International journal of general medicine · 2023Article
- Developing the novel diagnostic model and potential drugs by integrating bioinformatics and machine learning for aldosterone-producing adenomas.Frontiers in molecular biosciences · 2023Article
- Recent advances in conventional and unconventional vesicular secretion pathways in the tumor microenvironment.Journal of biomedical science · 2022Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRAB GTPases are important in the regulation of membrane trafficking and cell movement. Recently, exocytic RABs have received increasing attention in cancer research. However, the functional roles of exocytic RABs in colorectal carcinogenesis remain to be elucidated.
methodsImmunohistochemistry analysis of a microarray containing 215 colorectal adenocarcinoma tissues was used to identify the association between exocytic RABs and patient prognosis. Complementary functional RAB3C overexpression and knockdown experiments were performed. The molecular mechanism of RAB3C in inducing colon cancer cell metastasis was determined.
resultsHigh RAB3C expression in patients was found to be significantly associated with advanced pathological stage, distant metastasis and poor prognosis. Multivariate analyses showed that high RAB3C expression was an independent prognostic marker in overall (P = 0.001) and disease-free survival (P < 0.001). Furthermore, our experimental results showed an increase in the migration and invasion ability of RAB3C-overexpressing colon cancer cells and increased metastatic nodules in a mouse metastasis model. The effect of RAB3C-overexpressing cell-conditioned medium was found to significantly promote the migration ability of parental colon cancer cells, thus suggesting that the promotion of migration is exocytosis dependent. Upregulation of other exocytic RABs was also seen in RAB3C-overexpressing cells. Through microarray and proteomics analyses, increased production of multiple cytokines was observed in RAB3C-overexpressing cell lines, and the IL-6 pathway was the top pathway whose members exhibited gene expression changes after RAB3C overexpression, according to Ingenuity Pathway Analysis. Blocking IL-6 with IL-6 antibody treatment or IL-6 knockdown significantly inhibited the migration potential of RAB3C-overexpressing colon cancer cells. In addition, IL-6 was found to induce STAT3 phosphorylation in RAB3C-overexpressing colon cancer cells, thus promoting migration. Ruxolitinib, a JAK2 inhibitor, was found to significantly inhibit RAB3C-induced colon cancer cell migration.
conclusionsOur study revealed that RAB3C overexpression promotes tumor metastasis and is associated with poor prognosis in colorectal cancer, through modulating the ability of cancer cells to release IL-6 through exocytosis and activate the JAK2-STAT3 signaling pathway. These results further suggest that inhibition of STAT3 phosphorylation in the RAB3C-IL-6-STAT3 axis by using Ruxolitinib may be a new therapeutic strategy to combat metastatic colon cancers.
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