期刊论文详细信息
Cancers
Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts
Hanna Najgebauer1  ChristopherM. Sanderson1  Andrea Varro1  AndrewF. Jarnuczak2 
[1] Department of Cellular and Molecular Physiology, University of Liverpool, Crown Street, Liverpool L69 3BX, UK;European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK;
关键词: cancer-associated myofibroblasts;    hypoxia;    tumour microenvironment;    gene expression;    secretome;    transcriptomics;    proteomics;    gastric cancer;    omics;   
DOI  :  10.3390/cancers11020263
来源: DOAJ
【 摘 要 】

Although hypoxia is known to contribute to several aspects of tumour progression, relatively little is known about the effects of hypoxia on cancer-associated myofibroblasts (CAMs), or the consequences that conditional changes in CAM function may have on tumour development and metastasis. To investigate this issue in the context of gastric cancer, a comparative multiomic analysis was performed on populations of patient-derived myofibroblasts, cultured under normoxic or hypoxic conditions. Data from this study reveal a novel set of CAM-specific hypoxia-induced changes in gene expression and secreted proteins. Significantly, these signatures are not observed in either patient matched adjacent tissue myofibroblasts (ATMs) or non-cancer associated normal tissue myofibroblasts (NTMs). Functional characterisation of different myofibroblast populations shows that hypoxia-induced changes in gene expression not only enhance the ability of CAMs to induce cancer cell migration, but also confer pro-tumorigenic (CAM-like) properties in NTMs. This study provides the first global mechanistic insight into the molecular changes that contribute to hypoxia-induced pro-tumorigenic changes in gastric stromal myofibroblasts.

【 授权许可】

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