Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1
By Chi Lam Au Yeung, N. Co, T. Tsuruga, T. Yeung, Suet-Ying Kwan, Cecilia S. Leung, Yong Li, Edward S. Lu, Kenny Kwan, K. Wong and 3 more. Nature Communications, 2016
689 citations recorded by the source corpus.
Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the omental stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, using next-generation sequencing technology, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian cancer cells. Functional studies reveal that miR21 is transferred from CAAs or CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1. These data suggest that the malignant phenotype of metastatic ovarian cancer cells can be altered by miR21 delivered by exosomes derived from neighbouring stromal cells in the omental tumour microenvironment, and that inhibiting the transfer of stromal-derived miR21 is an alternative modality in the treatment of metastatic and recurrent ovarian cancer. The tumor microenviroment can influence cancer progression and response to therapy. In this study, the authors show that miR21 is transferred through exosomes from cancer-associated fibroblasts and adipocytes to ovarian cancer cells where it modulates drug resistance by its direct target APAF1.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/a4a57c47c4f80bbe393b9f397d313b778c34d8c2
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Citations in the corpus
- Extracellular vesicles in cancer: cell-to-cell mediators of metastasis (2016, background): “Interestingly, exosomal miR-21 transfer from cancer-associated adipocytes and fibroblasts to ovarian cancer cells suppresses apoptosis and confers chemoresistance by binding to APAF1 (Au Yeung et al., 2016).”
- Carcinoma-associated fibroblasts promote the stemness and chemoresistance of colorectal cancer by transferring exosomal lncRNA H19 (2018, background): “As the main infiltrated non-lymphocytes in tumor stroma, CAFs promote tumor cell proliferation, cell invasion, angiogenesis and chemoresistance by secreting a secretome that includes CAF-specific proteins, cytokines and extracellular matrix [6-8].”