How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations.

Abstract:

:Chronic exposure to intraperitoneal asbestos triggered a marked response in the mesothelium well before tumor development. Macrophages, mesothelial precursor cells, cytokines, and growth factors accumulated in the peritoneal lavage. Transcriptome profiling revealed YAP/TAZ activation in inflamed mesothelium with further activation in tumors, paralleled by increased levels of cells with nuclear YAP/TAZ. Arg1 was one of the highest upregulated genes in inflamed tissue and tumor. Inflamed tissue showed increased levels of single-nucleotide variations, with an RNA-editing signature, which were even higher in the tumor samples. Subcutaneous injection of asbestos-treated, but tumor-free mice with syngeneic mesothelioma tumor cells resulted in a significantly higher incidence of tumor growth when compared to naïve mice supporting the role of the environment in tumor progression.

journal_name

Oncogene

journal_title

Oncogene

authors

Rehrauer H,Wu L,Blum W,Pecze L,Henzi T,Serre-Beinier V,Aquino C,Vrugt B,de Perrot M,Schwaller B,Felley-Bosco E

doi

10.1038/s41388-018-0153-z

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

2645-2659

issue

20

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-018-0153-z

journal_volume

37

pub_type

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