Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts



Najgebauer, Hanna, Jarnuczak, Andrew E, Varro, Andrea and Sanderson, Christopher M ORCID: 0000-0002-7301-3537
(2019) Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts. CANCERS, 11 (2).

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: cancer-associated myofibroblasts, hypoxia, tumour microenvironment, gene expression, secretome, transcriptomics, proteomics, gastric cancer, omics
Depositing User: Symplectic Admin
Date Deposited: 28 Mar 2019 15:36
Last Modified: 20 Aug 2022 03:13
DOI: 10.3390/cancers11020263
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3035216