Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Philip P. Ip
  • Shengtao Zhou
  • Alice S. Wong

Detail(s)

Original languageEnglish
Pages (from-to)4227–4240
Journal / PublicationOncogene
Volume39
Issue number21
Online published13 Apr 2020
Publication statusPublished - 21 May 2020

Abstract

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.

Citation Format(s)

Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites. / Kan, Tongtong; Wang, Wei; Ip, Philip P.; Zhou, Shengtao; Wong, Alice S.; Wang, Xin; Yang, Mengsu.

In: Oncogene, Vol. 39, No. 21, 21.05.2020, p. 4227–4240.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal