Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905.
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905.
Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):E9580-E9589. doi: 10.1073/pnas.1807751115. Epub 2018 Sep 26.
Triple-negative breast cancer (TNBC) accounts for a disproportionately high number of deaths due to a lack of targeted therapies and an increased likelihood of distant recurrence. Estrogen receptor beta (ERβ), a well-characterized tumor suppressor, is expressed in 30% of TNBCs, and its expression is associated with improved patient outcomes. We demonstrate that therapeutic activation of ERβ elicits potent anticancer effects in TNBC through the induction of a family of secreted proteins known as the cystatins, which function to inhibit canonical TGFβ signaling and suppress metastatic phenotypes both in vitro and in vivo. These data reveal the involvement of cystatins in suppressing breast cancer progression and highlight the value of ERβ-targeted therapies for the treatment of TNBC patients.
三阴性乳腺癌（TNBC）由于缺乏靶向治疗和远处复发的可能性增加，导致死亡人数不成比例地高。雌激素受体β（ERβ）是一种特征明确的肿瘤抑制因子，在 30%的 TNBC 中表达，其表达与患者预后的改善相关。我们证明，通过诱导一组称为组织蛋白酶的分泌蛋白，治疗性激活 ERβ 在 TNBC 中产生强大的抗癌作用，这些蛋白的功能是抑制经典的 TGFβ 信号，并在体外和体内抑制转移表型。这些数据揭示了组织蛋白酶在抑制乳腺癌进展中的作用，并强调了 ERβ 靶向治疗在治疗 TNBC 患者中的价值。
