RAB27B-activated secretion of stem-like tumor exosomes delivers the biomarker microRNA-146a-5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer

Wei Chung Cheng, Tsai Tsen Liao, Chun Chi Lin, Lan Ting Emily Yuan, Hsin Yi Lan, Hung Hsin Lin, Hao Wei Teng, Hsin Chuan Chang, Chi Hung Lin, Chih Yung Yang, Shih Ching Huang, Jeng Kai Jiang, Shung Haur Yang, Muh Hwa Yang, Wei Lun Hwang

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8 Citations (Scopus)

Abstract

The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β-catenin/Tcf-4-activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA-146a-5p (miR-146a) is the major miRNA in CRCSC exosomes and exosomal miR-146a promotes stem-like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR-146a expression in serum exhibits higher miR-146a High /Numb Low CRCSC traits, an increased number of tumor-filtrating CD66(+) neutrophils and a decreased number of tumor-infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome-mediated stemness expansion.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • cancer stem cells
  • exosome heterogeneity
  • microRNA biomarker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Cheng, W. C., Liao, T. T., Lin, C. C., Yuan, L. T. E., Lan, H. Y., Lin, H. H., Teng, H. W., Chang, H. C., Lin, C. H., Yang, C. Y., Huang, S. C., Jiang, J. K., Yang, S. H., Yang, M. H., & Hwang, W. L. (2019). RAB27B-activated secretion of stem-like tumor exosomes delivers the biomarker microRNA-146a-5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer. International Journal of Cancer. https://doi.org/10.1002/ijc.32338