BRCA1 mutation promotes sprouting angiogenesis in inflammatory cancer-associated fibroblast of triple-negative breast cancer
| Title: | BRCA1 mutation promotes sprouting angiogenesis in inflammatory cancer-associated fibroblast of triple-negative breast cancer |
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| Authors: | Chae Min Lee, Yeseong Hwang, Jae Woong Jeong, Minki Kim, Janghee Lee, Soong June Bae, Sung Gwe Ahn, Sungsoon Fang |
| Source: | Cell Death Discovery, Vol 10, Iss 1, Pp 1-13 (2024) |
| Publisher Information: | Nature Publishing Group, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens LCC:Cytology |
| Subject Terms: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671 |
| More Details: | Abstract Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with inferior outcomes owing to its low treatment response and high invasiveness. Based on abundant cancer-associated fibroblasts (CAFs) and frequent mutation of breast cancer-associated 1 (BRCA1) in TNBC, the characteristics of CAFs in TNBC patients with BRCA1 mutation compared to wild-type were investigated using single-cell analysis. Intriguingly, we observed that characteristics of inflammatory CAFs (iCAFs) were enriched in patients with BRCA1 mutation compared to the wild-type. iCAFs in patients with BRCA1 mutation exhibited outgoing signals to endothelial cells (ECs) clusters, including chemokine (C-X-C motif) ligand (CXCL) and vascular endothelial growth factor (VEGF). During CXCL signaling, the atypical chemokine receptor 1 (ACKR1) mainly interacts with CXCL family members in tumor endothelial cells (TECs). ACKR1-high TECs also showed high expression levels of angiogenesis-related genes, such as ANGPT2, MMP1, and SELE, which might lead to EC migration. Furthermore, iCAFs showed VEGF signals for FLT1 and KDR in TECs, which showed high co-expression with tip cell marker genes, including ZEB1 and MAFF, involved in sprouting angiogenesis. Moreover, BRCA1 mutation patients with relatively abundant iCAFs and tip cell gene expression exhibited a limited response to neoadjuvant chemotherapy, including cisplatin and bevacizumab. Importantly, our study observed the intricate link between iCAFs-mediated angiogenesis and chemoresistance in TNBC with BRCA1 mutation. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2058-7716 99221268 |
| Relation: | https://doaj.org/toc/2058-7716 |
| DOI: | 10.1038/s41420-023-01768-5 |
| Access URL: | https://doaj.org/article/8b992212685543c3abd95aa3b7f177e2 |
| Accession Number: | edsdoj.8b992212685543c3abd95aa3b7f177e2 |
| Database: | Directory of Open Access Journals |
| ISSN: | 20587716 99221268 |
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| DOI: | 10.1038/s41420-023-01768-5 |
| Published in: | Cell Death Discovery |
| Language: | English |