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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
Author(s) -
Cheng WeiChung,
Liao TsaiTsen,
Lin ChunChi,
Yuan LanTing Emily,
Lan HsinYi,
Lin HungHsin,
Teng HaoWei,
Chang HsinChuan,
Lin ChiHung,
Yang ChihYung,
Huang ShihChing,
Jiang JengKai,
Yang ShungHaur,
Yang MuhHwa,
Hwang WeiLun
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32338
Subject(s) - microvesicles , exosome , microrna , tumor microenvironment , cancer research , biology , carcinogenesis , tumor progression , cancer stem cell , stem cell , microbiology and biotechnology , cancer , genetics , tumor cells , gene
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.