Mir-30c Blocks Tumor Cell Homotypic Aggregation And Promotes Anoikis To Prevent Breast Cancer Metastasis

Circulating tumor cells (CTCs) are considered the seeds of distant metastasis, and may be a predictor of poor prognosis in patients with metastatic breast cancers. Compared to single CTCs, clusters of multiple CTCs possess higher metastatic capacity in mouse breast cancer models, indicating that aggregation increases the survival of CTCs in the circulation. However, the molecular mechanisms by which clustered CTCs mediate tumor cell survival are unclear. In this study, we found that miR-30c, which has been identified as an anti-metastatic microRNAs, inhibited primary breast cancer cell homotypic aggregation in vitro by real-time monitoring. Interestingly, only aggregated but not single tumor cells can survive during culture. The death of dissociated primary tumor cells in vitro is caused by anoikis, a form of programmed cell death which is induced by detachment of anchorage-dependent cells from the surrounding extracellular matrix. Therefore, the role of miR-30c in anoikis was determined by culturing breast cancer cells in poly-hema coated plates. We found that miR-30c promoted anoikis, evaluated by Annexin-V staining and caspase3/7 activity. Mechanistic studies indicated that inhibition of Vimentin (Vim), a positive regulator of epithelial-to-mesenchymal transition (EMT), was required for miR-30c induced anoikis. In vivo, lung metastasis was inhibited by miR-30c after tail vein injection of miR-30c over-expressed cells. In summary, our findings provide the new insights into the mechanisms of miR-30c-mediated metastasis inhibition and suggest that targeting CTC clusters could be a novel strategy to prevent metastasis. Citation Format: Xia Liu, Beijie Yu, Wenjing Chen, Huiping Liu. miR-30c blocks tumor cell homotypic aggregation and promotes anoikis to prevent breast cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1909.