机构：[1]Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China[2]Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China[3]Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second Hospital and State Key Laboratory of Biotherapy/Collaborative Innovation Center, West China Hospital, Sichuan University, Chengdu, China四川大学华西医院[4]School of Biological Sciences, The University of Hong Kong, Hong Kong, China[5]Key Laboratory of Biochip Technology, Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China
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.
基金：
This work was supported by grants from the General Research Fund (CityU_11303815) and the Collaborative Research Fund (CRF/1013-15G) of Hong Kong Research Grant Council, the Guangdong Frontier and Key Technology Development Fund (2017B020226001) of Guangdong Province, PR China, and the Knowledge Innovation Program (JCYJ20150601102053070) of Shenzhen Municipality,PR China.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|1 区医学
小类|1 区生化与分子生物学1 区肿瘤学1 区遗传学2 区细胞生物学
最新[2023]版：
大类|1 区医学
小类|1 区生化与分子生物学1 区遗传学2 区细胞生物学2 区肿瘤学
第一作者：
第一作者机构：[1]Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
通讯作者：
通讯机构：[1]Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China[5]Key Laboratory of Biochip Technology, Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China
推荐引用方式(GB/T 7714)：
Tongtong Kan,Wei Wang,Philip P. Ip,et al.Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites.[J].Oncogene.2020,39(21):4227-4240.doi:10.1038/s41388-020-1288-2.
APA：
Tongtong Kan,Wei Wang,Philip P. Ip,Shengtao Zhou,Alice S. Wong...&Mengsu Yang.(2020).Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites..Oncogene,39,(21)
MLA：
Tongtong Kan,et al."Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites.".Oncogene 39..21(2020):4227-4240
医学