乳腺癌干细胞（Breast Cancer Stem Cells, BCSCs）是导致肿瘤发生、耐药、复发及转移的主要原因。研究表明TRB3（Tribbles homolog 3）不仅参与肿瘤的侵袭转移，而且与肿瘤病人不良预后呈正相关。我们发现BCSCs表达高水平TRB3，抑制TRB3表达能降低BCSCs体外形成微球的能力，这是因为转录因子FoxO1介导TRB3促进干性因子Sox2基因转录。本项目拟深入研究TRB3/AKT1相互作用调节FoxO1-Sox2的表达和功能，以确定TRB3调节BCSCs的作用机制和促进乳腺癌发生发展的重要作用。我们将在此基础上，筛选抑制TRB3/AKT1相互作用的螺旋肽并研究螺旋肽是否具有抑制BCSCs功能的作用及抗乳腺癌的治疗作用。本项目将有助于我们深入理解TRB3 调节BCSCs功能，促进乳腺癌发展的机制，为开发新的治疗乳腺癌复发及转移药物提供理论和实验依据。

Breast Cancer Stem Cells (BCSCs) is the main reason to cause drug resistance, tumor recurrence and metastasis. Recent studies show that TRB3 (Tribbles homolog 3) involved in tumor invasion and metastasis, and also the expression level of TRB3 correlates aggressive breast cancer progression. Here, we found enhanced expression of TRB3 in BCSCs, silencing TRB3 inhibited the tumor mammospheres formation in vitro, transcriptional factor FoxO1 played a key role during TRB3 promoting stemness factor SOX2 gene transcription. We proposed to investigate the molecular mechanism of TRB3 regulating BCSCs, indentify the role of TRB3/AKT1 interaction in BCSCs, confirm that TRB3 play an important role to accelerate breast cancer disease progression, screen the α-helix peptides the blocking effects for TRB3/AKT1 interaction, and verify the inhibit effects of these peptides for breast cancer stemness. The proposed studies will provide new insights into the molecular pathogenesis of breast cancer stemness and identify the therapeutic targets and lead compounds for breast cancer recurrence and metastasis.