Faculty, Staff and Student Publications
Language
English
Publication Date
4-21-2023
Journal
iScience
DOI
10.1016/j.isci.2023.106482
PMID
37091228
PMCID
PMC10119611
PubMedCentral® Posted Date
3-21-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Extracellular vesicles (EVs) regulate the tumor microenvironment by facilitating transport of biomolecules. Despite extensive investigation, heterogeneity in EV secretion among cancer cells and the mechanisms that support EV secretion are not well characterized. We developed an integrated method to identify individual cells with differences in EV secretion and performed linked single-cell RNA-sequencing on cloned single cells from the metastatic breast cancer cells. Differential gene expression analyses identified a four-gene signature of breast cancer EV secretion: HSP90AA1, HSPH1, EIF5, and DIAPH3. We functionally validated this gene signature by testing it across cell lines with different metastatic potential in vitro. Analysis of the TCGA and METABRIC datasets showed that this signature is associated with poor survival, invasive breast cancer types, and poor CD8+ T cell infiltration in human tumors. We anticipate that our method for directly identifying the molecular determinants of EV secretion will have broad applications across cell types and diseases.
Keywords
Biotechnology, Cancer systems biology, Cancer, Transcriptomics
Published Open-Access
yes
Recommended Citation
Fathi, Mohsen; Martinez-Paniagua, Melisa; Rezvan, Ali; et al., "Identifying Signatures of Ev Secretion in Metastatic Breast Cancer Through Functional Single-Cell Profiling" (2023). Faculty, Staff and Student Publications. 5457.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5457
Graphical Abstract
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons