CD10+GPR77+ Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness
Open accessAbstract
Carcinoma-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in tumor microenvironment that are critically involved in cancer progression. Here, we demonstrate that two cell-surface molecules, CD10 and GPR77, specifically define a CAF subset correlated with chemoresistance and poor survival in multiple cohorts of breast and lung cancer patients. CD10+GPR77+ CAFs promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs). Mechanistically, CD10+GPR77+ CAFs are driven by persistent NF-κB activation via p65 phosphorylation and acetylation, which is maintained by complement signaling via GPR77, a C5a receptor. Furthermore, CD10+GPR77+ CAFs promote successful engraftment of patient-derived xenografts (PDXs), and targeting these CAFs with a neutralizing anti-GPR77 antibody abolishes tumor formation and restores tumor chemosensitivity. Our study reveals a functional CAF subset that can be defined and isolated by specific cell-surface markers and suggests that targeting the CD10+GPR77+ CAF subset could be an effective therapeutic strategy against CSC-driven solid tumors.
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An NF-κB-driven subset of CAFs expressing GPR77 and CD10 promotes stemness and chemoresistance within breast cancer cells.
“Another study reported an NF-κB-driven subset of CAFs expressing GPR77 and CD10, which promote ‘stemness’ and chemoresistance within breast cancer cells135.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [135]
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- Authors
- Su, S., Chen, J., Yao, H., Liu, J., Yu, S., Lao, L., Wang, M., Luo, M., Xing, Y., Chen, F., Huang, D., Zhao, J., Yang, L., Liao, D., Su, F., Li, M., Liu, Q., & Song, E.
- Affiliations
- Sun Yat-sen University (CN)
- Corresponding author
- Song, Erwei
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 172
- Issue
- 4
- Pages
- 841-856.e16
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2785291766
- Cited by
- 1,230
- References
- 4
- Citations by year
- 2026: 78 · 2025: 127 · 2024: 155 · 2023: 179 · 2022: 193 · 2021: 213 · 2020: 145 · 2019: 98 · 2018: 41
- FWCI
- 46.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research
- Development Program of China (2017YFA0106300, 2016YFC1302300)
- National Natural Science Foundation of China (81622036, 81472468, 81672614, 81720108029, 81621004, 81490750, 81230060, 81442009, 81372819, 81572596, U1601223, 81672620)
- Science Foundation of Guangdong Province (2016A030306023, 2014A030313094, S2012030006287, 2016B030229004, 2015B050501004, 2017A030313878, 2017A030313828)
- Tip-top Scientific and Technical Innovative Youth Talents of Guangdong special support program (2016TQ03R553)
- Guangzhou science and technology project (201710010083, 2014J4100170, 201704020131)
- Guangzhou Science Technology and Innovation Commission (201508020008, 201508020249)
- Guangdong Science and Technology Department (2015B050501004)
- Translational medicine public platform of Guangdong Province (4202037)
- Guangdong Department of Science & Technology Translational Medicine Center (2011A080300002)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- cancer-associated fibroblasts, CD10, cancer stem cells, chemoresistance, NF-κB activation, C5a receptor, tumor microenvironment, breast cancer, lung cancer, patient-derived xenografts
- MeSH terms
- A549 Cells, Cell Transformation, Neoplastic, Fibroblasts, Humans, Neoplasm Proteins, Neoplasms, Neoplastic Stem Cells, Neprilysin, Drug Resistance, Neoplasm, Receptors, Chemokine, Receptor, Anaphylatoxin C5a, Tumor Microenvironment, MCF-7 Cells
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