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Int J Biol Sci 2018; 14(14):2094-2102. doi:10.7150/ijbs.28288

Research Paper

Exosomes Derived from Hypoxic Colorectal Cancer Cells Transfer Wnt4 to Normoxic Cells to Elicit a Prometastatic Phenotype

Zhe Huang, Mingli Yang, Yunze Li, Fan Yang, Yong Feng

Department of 11th general surgery, Shengjing Hospital of China medical university, Shenyang, China.

Abstract

Hypoxia is the most common characteristic of solid tumours driving cancer metastasis. Cancer cells release exosomes with various functions into the tumour microenvironment during cancer progression. However, the roles and associated mechanisms of hypoxic colorectal cancer (CRC) cell-derived exosomes remain poorly understood. Here, we found that exosomes secreted by hypoxic CRC cells promoted the migration and invasion abilities of normoxic CRC cells. Inhibition of exosome secretion by GW4869 reduced hypoxic exosome-mediated migration and invasion of normoxic CRC cells. Furthermore, we found that these hypoxic exosomes contained Wnt4 depending on HIF1α. Exosomal Wnt4 mediated hypoxic exosome-mediated migration and invasion of normoxic CRC cells. Moreover, exosomal Wnt4 enhanced β-catenin translocation to the nucleus in normoxic CRC cells. The activation of β-catenin signalling was important for the migration and invasion of normoxic CRC cells, which was eliminated by treatment with the β-catenin inhibitor ICG-001. Taken together, the results of our study indicate that hypoxia may stimulate tumour cells to release Wnt4-rich exosomes that are delivered to normoxic cells to enhance prometastatic behaviours, which might provide new targets for CRC treatment.

Keywords: colorectal cancer, hypoxia, exosome, prometastatic, Wnt4, β-catenin

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Huang Z, Yang M, Li Y, Yang F, Feng Y. Exosomes Derived from Hypoxic Colorectal Cancer Cells Transfer Wnt4 to Normoxic Cells to Elicit a Prometastatic Phenotype. Int J Biol Sci 2018; 14(14):2094-2102. doi:10.7150/ijbs.28288. Available from http://www.ijbs.com/v14p2094.htm