致癌的细胞表面膜蛋白贡献于癌干细胞（CSCs）的表型和功能特征。我们采用了近距离标记蛋白质组学的方法，定量分析CD147与CSCs密切接近的细胞表面膜蛋白质。此外，我们将CSCs与非CSCs进行了比较，以识别与CD147密切相互作用的CSC特异性细胞表面膜蛋白，并揭示出CD147与CD276之间的侧面相互作用隐藏在CSCs的脂 rafts微区里，使CSCs对多种癌症类型，包括转移性乳腺癌常用化疗药物docetaxel产生耐药性。此外，我们研究了接受化疗的HER2阳性乳腺癌（BC）和三阴性乳腺癌患者中CD147和CD276共表达的临床相关性。我们观察到CD147和CD276表达患者的疾病无复发生存率和总体生存率较差（p = 0.04和0.08）。随后独立的HER2阳性BC队列的免疫组化分析支持了CD147和CD276共表达与化疗反应差的关联。综上所述，我们的研究表明CD147与其临近伴侣（如CD276）之间的侧面相互作用可能作为BC中的不良预后因子以及BC干细胞的关键表型决定因子的预测标志物。© 2023. Springer Nature Limited.

Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We employed a proximity-labeling proteomic approach to quantitatively analyze the cell-surface membrane proteins in close proximity to CD147 in CSCs. Furthermore, we compared CSCs to non-CSCs to identify CSC-specific cell-surface membrane proteins that are closely interact with CD147 and revealed that lateral interaction between CD147 and CD276 concealed within the lipid raft microdomain in CSCs, confers resistance to docetaxel, a commonly used chemotherapy agent for various cancer types, including metastatic breast cancer. Moreover, we investigated the clinical relevance of CD147 and CD276 co-expression in HER2+ breast cancer (BC) and triple-negative breast cancer patients who underwent chemotherapy. We observed poor disease-free survival and Overall survival rates in patients of CD147 and CD276 (p = 0.04 and 0.08, respectively). Subsequent immunohistochemical analysis in independent cohorts of HER2+ BC support for the association between co-expression of CD147 and CD276 and a poor response to chemotherapy. Collectively, our study suggests that the lateral interaction between CD147 and its proximal partners, such as CD276, may serve as a poor prognostic factor in BC and a predictive marker for the critical phenotypic determinant of BC stemness.© 2023. Springer Nature Limited.