Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFβ-dependent Smad/YAP/TAZ signaling.

Abstract:

:Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-β (TGFβ)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFβ through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFβ axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Qi YJ,Jiao YL,Chen P,Kong JY,Gu BL,Liu K,Feng DD,Zhu YF,Ruan HJ,Lan ZJ,Liu QW,Mi YJ,Guo XQ,Wang M,Liang GF,Lamont RJ,Wang H,Zhou FY,Feng XS,Gao SG

doi

10.1371/journal.pbio.3000825

subject

Has Abstract

pub_date

2020-09-04 00:00:00

pages

e3000825

issue

9

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-20-00010

journal_volume

18

pub_type

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