PloS one, 2021-12, Vol.16 (12), p.e0260800-e0260800
2021
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- Autor(en) / Beteiligte
- Titel
- The neutrophil protein CD177 is a novel PDPN receptor that regulates human cancer-associated fibroblast physiology
- Ist Teil von
- PloS one, 2021-12, Vol.16 (12), p.e0260800-e0260800
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The cancer-associated fibroblast (CAF) marker podoplanin (PDPN) is generally correlated with poor clinical outcomes in cancer patients and thus represents a promising therapeutic target. Despite its biomedical relevance, basic aspects of PDPN biology such as its cellular functions and cell surface ligands remain poorly uncharacterized, thus challenging drug development. Here, we utilize a high throughput platform to elucidate the PDPN cell surface interactome, and uncover the neutrophil protein CD177 as a new binding partner. Quantitative proteomics analysis of the CAF phosphoproteome reveals a role for PDPN in cell signaling, growth and actomyosin contractility, among other processes. Moreover, cellular assays demonstrate that CD177 is a functional antagonist, recapitulating the phenotype observed in PDPN-deficient CAFs. In sum, starting from the unbiased elucidation of the PDPN co-receptome, our work provides insights into PDPN functions and reveals the PDPN/CD177 axis as a possible modulator of fibroblast physiology in the tumor microenvironment.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0260800Titel-ID: cdi_plos_journals_2608084051
- Format
- –
- Schlagworte
- Actomyosin, Analysis, Apoptosis, Biology and Life Sciences, Biomarkers, Tumor - genetics, Biomarkers, Tumor - metabolism, Cancer, Cancer-Associated Fibroblasts - immunology, Cancer-Associated Fibroblasts - metabolism, Cancer-Associated Fibroblasts - pathology, Cell cycle, Cell Proliferation, Cell signaling, Cell surface, Colorectal Neoplasms - genetics, Colorectal Neoplasms - immunology, Colorectal Neoplasms - metabolism, Colorectal Neoplasms - pathology, Contractility, Drug development, Fibroblasts, Gene Expression Regulation, Neoplastic, GPI-Linked Proteins - genetics, GPI-Linked Proteins - metabolism, Humans, Immunology, Immunotherapy, Isoantigens - genetics, Isoantigens - metabolism, Leukocytes (neutrophilic), Ligands, Mass spectrometry, Medicine and Health Sciences, Membrane Glycoproteins - genetics, Membrane Glycoproteins - metabolism, Membrane proteins, Microscopy, Neutrophils, Neutrophils - immunology, Neutrophils - metabolism, Phenotypes, Physiology, Prognosis, Protein binding, Proteins, Proteomics, Receptors, Cell Surface - genetics, Receptors, Cell Surface - metabolism, Scientific imaging, Survival Rate, Therapeutic targets, Tumor Cells, Cultured, Tumor Microenvironment, Tumors