Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis

• Published in: Scientific reports Vol. 13; no. 1; p. 14242
• Main Authors: Seo, Yu Ri, Lee, Junghyeon, Ryu, Han Suk, Kim, EunHee G, Kim, So Hyun, Jeong, Jieun, Jung, Hyeryeon, Jung, YeoJin, Kim, Han Byeol, Jo, Yeon Hui, Kim, Yeong Dong, Jin, Min-Sun, Lee, Yong Yook, Kim, Kristine M, Yi, Eugene C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 30.08.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: Breast cancer; CD147 antigen; Cell surface; Chemotherapy; ErbB-2 protein; Membrane proteins; Metastases; Proteins; Proteomes; Proteomics; Stem cells; Survival
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-41416-7

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.