三阴性乳腺癌(TNBC)无法实行靶向及内分泌治疗，与其他亚型乳腺癌相比恶性度最高。传统化疗是其主要治疗手段，患者一旦发生耐药则面临无药可治的恶性局面，预后极差。针对TNBC耐药分子机制寻找相应的逆转途径及治疗靶点已成为亟待解决的关键科学问题。我们前期研究证实雌激素相关受体（ERR）在TNBC发展中起重要促进作用，发现其亚型ERRγ高表达于TNBC耐药株，其敲除或靶向抑制可有效提升化疗敏感性，并初步揭示ERRγ可靶向ABCB1、miR-200b并与NF-κB形成复合体介导耐药，提示其可作为逆转TNBC耐药的重要靶点。本研究拟进一步确证ERRγ介导TNBC化疗耐药的体内外作用，解析其参与化疗耐药的可能下游分子机制，探讨其在TNBC耐药过程中的高表达、共激活及转录上调机制，并系统评价以其为靶点提升TNBC化疗敏感度的可行性，以期为克服TNBC临床耐药提供了新的具有重大潜力的作用靶点和治疗策略。

Triple negative breast cancer (TNBC) patients do not benefit from endocrine therapy and show a poorer prognosis than patients with ER-positive tumor because endocrine and targeted therapy has no significant clinical effect. Chemotherapy is the major treatment approach for TNBC. Once the occurrence of chemoresistance, TNBC patients have no candidate drugs, which lead to the prognosis is extremely poor. It is an urgent need to explore new targets and therapy methods to elevate the drug sensitivity of chemoresistance TNBC patients. Our previous studies revealed that estrogen related receptor (ERR) trigger the development of TNBC cells, and found that the expression of ERRγ is significantly increased in TNBC chemoresistant cell lines. Furthermore, the inhibitor or si-ERRγ can significantly increase the doxorubicin (DOX) and Taxol sensitivity of TNBC chemoresistant cell lines. This might be due to that ERRγ can regulate ABCB1 and miR-200b and form complex with NF-κB in TNBC chemoresistant cell lines. The present study proposal will ensure that ERRγ mediates the chemo-sensitivity of TNBC cells, investigate its up and down stream signaling, and then evaluate the feasibility to treatment chemoresistant TNBC on the basis of targeted ERRγ. Our study will break our cognitive limitation that there is no drug target for chemoresistant TNBC treatment and afford new approach to therapy TNBC.