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Desulfovibrio Vulgaris Flagellin Induces Epithelial-Mesenchymal Transition of Colorectal Cancer through LRRC19/TRAF6/TAK1 Pathway

Listed in NCBI GEO

Dysbiosis of microbiota derived from mucosa and feces indicated the inseparable relationship between gut microbiota and colorectal cancer (CRC).

Description

However, the specific mechanisms underlying remain incompletely understood. We found that Desulfovibrio vulgaris (DSV) was upregulated in CRC animal models and patient databases.

We aimed to further investigate the role of DSV and detected a high level in the feces and tissues of CRC patients. Moreover, DSV gavage administration promoted colonocyte proliferation in germ-free mice. Subsequently, we identified, synthesized, and purified the Desulfovibrio vulgaris flagellin (DVF) to explore the underlying mechanisms of DSV pathogenicity in CRC.

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DVF promoted proliferation, migration, and invasion in CRC cells. Transcriptome sequencing uncovered that epithelial-mesenchymal transition (EMT)-associated genes and tumor-related signaling pathways were enriched in the DVF-treated group. DVF could induce EMT in CRC cells and xenograft models separately, specifically manifested by downregulation of E-cadherin and upregulation of N-cadherin and Vimentin.

Mechanistically, DVF-dependent EMT required a novel functional transmembrane receptor called leucine-rich repeat containing 19 (LRRC19). The interaction between DVF and LRRC19 regulated the ubiquitination of TRAF6 instead of TRAF2, further promoting the ubiquitination of transforming growth factor-β-activated kinase 1 (TAK1) for autophosphorylation. The phosphorylation of TAK1 further facilitated the EMT.

Collectively, DVF promotes EMT dependent on the LRRC19/TRAF6/TAK1 pathway in CRC. Our research offers new insights into the mechanism of gut microbiota participating in the CRC and establishes a promising clinical therapy target.

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From keywords
Life Sciences
Inferred from text
Biochemistry and cell biology 68% · Cancer 75% · RNA sequencing 65% · Sequencing 75%
Provenance · 1 source records, 11 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE27104315 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].anzsrc:group:3101enrichment · NCBI GEOtaxonomy-embedding@1.1.0title+keywords+description (68%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title