STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells

• Published in: Cell death & disease 2021-01, Vol.12 (1), p.38-38, Article 38
• Main Authors: Pan, Shunli, Zhao, Xiaoxia, Shao, Chen, Fu, Bingjie, Huang, Yingying, Zhang, Ning, Dou, Xiaojing, Zhang, Zhe, Qiu, Yuling, Wang, Ran, Jin, Meihua, Kong, Dexin
• Format: Article
• Language: English
• Subjects: 13/51; 14/19; 38/77; 42/41; 631/67/2328; 692/699/67/327; 96/34; AKT protein; Angiogenesis; Antibodies; Biochemistry; Biomedical and Life Sciences; Breast cancer; Calcium (intracellular); Calcium signalling; Cell Biology; Cell Culture; Endothelial cells; Exosomes; Extracellular signal-regulated kinase; Immunology; Insulin; Insulin receptor substrate 1; Kinases; Life Sciences; miRNA; Protein kinase; Raf protein; Rapamycin; STIM1 protein; TOR protein; Umbilical vein
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-03304-0

Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca 2+ . Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca 2+ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently, we investigated the effect of exosomes from STIM1-knockout breast cancer MDA-MB-231 cells (Exo-STIM1-KO), and from SKF96365-treated MDA-MB-231 cells (Exo-SKF) on angiogenesis in human umbilical vein endothelial cells (HUVECs) and nude mice. The exosomes Exo-STIM1-KO and Exo-SKF inhibited tube formation by HUVECs remarkably. The miR-145 was increased in SKF96365 treated or STIM1-knockout MDA-MB-231 cells, Exo-SKF and Exo-STIM1-KO, and HUVECs treated with Exo-SKF or Exo-STIM1-KO. Moreover, the expressions of insulin receptor substrate 1 (IRS1), which is the target of miR-145, and the downstream proteins such as Akt/mammalian target of rapamycin (mTOR), Raf/extracellular signal regulated-protein kinase (ERK), and p38 were markedly inhibited in HUVECs treated with Exo-SKF or Exo-STIM1-KO. Matrigel plug assay in vivo showed that tumor angiogenesis was suppressed in Exo-STIM1-KO, but promoted when miR-145 antagomir was added. Taken together, our findings suggest that STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.