Stroma microvesicles mediated CSC evolution in endocrine resistant metastatic breast cancer.219 Autocrine IL-6/Stat3 signaling induces the proliferation of CAFs and the biogenesis of onco-miR221/222+ MVs; these MVs are taken up by estrogen receptor+ (ER+) breast cancer cells and lead to the potent suppression of ER signaling, resulting in Notch3 upregulation, which in turn sustains the self-renewal of CD133+ CSCs in an ER-independent manner. Here, ESR1 is linked to breast cancer.