Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites
| Autor: | Shengtao Zhou, Tongtong Kan, Alice S. Wong, Xin Wang, Philip P.C. Ip, Wei Wang, Mengsu Yang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition Carcinogenesis Cell Carcinoma Ovarian Epithelial Biology Metastasis 03 medical and health sciences 0302 clinical medicine Single-cell analysis Downregulation and upregulation Genetics Carcinoma medicine Humans Epithelial–mesenchymal transition Molecular Biology Ovarian Neoplasms Disseminated Tumor Cell Transition (genetics) Ascites medicine.disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Female Single-Cell Analysis |
| Zdroj: | Oncogene. 39:4227-4240 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/s41388-020-1288-2 |
| Popis: | Malignant ascites of epithelial ovarian cancer is a metastatic tumor microenvironment in which large amounts of disseminated single cells (DSCs) and disseminated tumor cell clusters (DTCCs) are commonly observed. The tumor cell clusters are known to be more aggressive than individual tumor cells in cancer metastasis; however, little is known about the mechanism. Applying single-cell epithelial-to-mesenchymal transition (EMT)-related transcriptional analysis in 120 DSCs and 195 intra-cluster cells from 27 DTCCs, we demonstrated that DTCCs were heterogeneous cellular units comprised of epithelial tumor cells, leukocytes, and cancer-associated fibroblasts (CAFs). Through the analysis of intra-DTCC heterogeneity, we identified that CAFs induced EMT of tumor cells via TGFβ signaling within the DTCC microenvironment. The activation of EMT program, in particular the upregulation of ZEB2, enabled the acquisition of additional chemoresistance and metastasis abilities of the intra-DTCC tumor cells, which resulted in the aggressiveness of DTCCs. |
| Databáze: | OpenAIRE |
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