Breast cancer-derived exosomal miR-105-5p facilitates the transformation of NFs into CAFs through LATS2-NF-κB signaling
- Xiaodi Ding 1, Zhimei Sheng 1,2, Jiayu Cui 1, Meimei Cui 1, Liying Zhang 1, Ruijun Feng 1, Yongming Wang 3, Wei Sun 2, Xiurong Zhang 4, Lihong Shi 5, Baogang Zhang 1
- Xiaodi Ding 1, Zhimei Sheng 1,2, Jiayu Cui 1
- 1Department of Pathology, Shandong Second Medical University, Weifang 261053, China.
- 2Affiliated Hospital of Shandong Second Medical University, Weifang 261041, China.
- 3Department of Thoracic Surgery, Translational Medical Center, Weifang Second People's Hospital (Weifang Respiratory Disease Hospital), Weifang 261041, China.
- 4Department of Pharmacology, Shandong Second Medical University, Weifang 261053, China.
- 5Department of Rehabilitation Medicine, Shandong Second Medical University, Weifang 261053, China.
- 0Department of Pathology, Shandong Second Medical University, Weifang 261053, China.
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View abstract on PubMed
Summary
This summary is machine-generated.Breast cancer exosomes transform normal fibroblasts into cancer-associated fibroblasts (CAFs) via miR-105-5p. This exosomal microRNA may be a therapeutic target to disrupt tumor microenvironment coevolution.
Area Of Science
- Oncology
- Cell Biology
- Molecular Medicine
Background
- The tumor microenvironment (TME) is crucial for cancer progression.
- Interactions between tumor cells and cancer-associated fibroblasts (CAFs) are key TME components.
- Targeting cell-cell communication within the TME offers oncotherapy potential.
Purpose Of The Study
- To investigate the role of breast cancer cell-derived exosomes in transforming normal fibroblasts (NFs) into CAFs.
- To identify specific molecules within exosomes responsible for this transformation.
- To explore the therapeutic potential of targeting this exosome-mediated process.
Main Methods
- Exosome isolation from breast cancer cell lines with varying metastatic potential.
- Co-culture experiments of NFs with breast cancer cell exosomes.
- Quantitative analysis of exosomal microRNA content (miR-105-5p).
- Luciferase reporter assays and Western blotting to assess gene expression (LATS2) and signaling pathways (NF-κB).
Main Results
- Breast cancer cell exosomes induce NF to CAF transformation, with higher metastatic cells releasing more potent exosomes.
- Exosomes from highly metastatic cells are enriched in miR-105-5p, which drives NF to CAF conversion.
- Exosomal miR-105-5p downregulates LATS2 and activates NF-κB signaling, promoting CAF activation and cancer cell epithelial-mesenchymal transition (EMT).
Conclusions
- Exosomal miR-105-5p facilitates breast cancer progression by transforming NFs into CAFs.
- This exosome-mediated pathway represents a novel mechanism of tumor microenvironment modulation.
- Targeting exosomal miR-105-5p offers a potential therapeutic strategy against breast cancer and CAF coevolution.
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