Exosomes Derived from Hypoxic Colorectal Cancer Cells Transfer Wnt4 to Normoxic Cells to Elicit a Prometastatic Phenotype
| Autor: | Yunze Li, Mingli Yang, Yong Feng, Fan Yang, Zhe Huang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Colorectal cancer Blotting Western colorectal cancer Exosomes Applied Microbiology and Biotechnology Exosome Tetraspanin 29 03 medical and health sciences Wnt4 Protein WNT4 medicine exosome Humans Secretion prometastatic Molecular Biology Ecology Evolution Behavior and Systematics Cell Proliferation Chemistry hypoxia Tetraspanin 30 Cell Biology Hypoxia (medical) β-catenin medicine.disease HCT116 Cells Phenotype Microvesicles digestive system diseases 030104 developmental biology Cancer cell Cancer research medicine.symptom Wnt4 Colorectal Neoplasms HT29 Cells Developmental Biology Research Paper Signal Transduction |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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