Fig. 7
From: Estradiol induces BDNF/TrkB signaling in triple-negative breast cancer to promote brain metastases
Current understanding of mechanisms underlying pro-metastatic effects of E2 in the brain. Reactive astrocytes express ERs and respond to pre-menopausal E2 levels by upregulating BDNF, EGF, and other growth factors and chemokines. BDNF can activate TrkB and/or EGFR in TNBC cells expressing these receptors, leading to activation of survival and invasive pathways. Paracrine action of E2 also leads to autocrine BDNF upregulation, supporting a positive feedback loop that enhances TrkB signaling in cancer cells. Full estrogen depletion and Trk inhibitors emerge as potential therapeutic alternatives in the prevention or treatment of TNBC BM
