Gemella morbillorum Promotes Colorectal Carcinogenesis: LPBDCP-Mediated Invasion Activates Ras Signaling and...

Area of Science:

• Microbiology
• Oncology
• Gastroenterology

Background:

• Gut microbiota dysbiosis is linked to colorectal cancer (CRC) development.
• Gemella morbillorum has been identified as a key bacterium associated with CRC.
• Understanding the mechanisms of G. morbillorum in CRC is crucial for therapeutic strategies.

Purpose of the Study:

• To elucidate the role and mechanisms of Gemella morbillorum in colorectal cancer tumorigenesis.
• To identify specific bacterial factors and host interactions involved in CRC promotion.
• To evaluate potential therapeutic targets for G. morbillorum-associated CRC.

Main Methods:

• Fecal metagenomic analysis and fluorescence in situ hybridization to identify and quantify G. morbillorum.
• In vitro and in vivo experiments using CRC cell lines and mouse models to assess oncogenic effects.
• RNA sequencing, co-immunoprecipitation, and mass spectrometry to identify molecular interactions and pathways.
• Genetic knockout strategies (LPBDCP, TMEM140, NDPD) to validate therapeutic targets.

Main Results:

• Gemella morbillorum is significantly enriched in CRC tumor tissues.
• G. morbillorum invades host cells via LPBDCP-TMEM140 interaction, triggering Ca2+ influx and activating PI3K-AKT-NF-κB and RAF-MEK-ERK pathways.
• Bacterial secretion of NDPD leads to p53 deacetylation and degradation, promoting cell proliferation and inhibiting apoptosis.
• Genetic disruption of LPBDCP, TMEM140, or NDPD abrogates the tumor-promoting effects of G. morbillorum.

Conclusions:

• Gemella morbillorum actively promotes colorectal cancer progression through specific invasion and enzymatic mechanisms.
• The LPBDCP-TMEM140 interaction and NDPD secretion represent critical pathways in G. morbillorum-driven tumorigenesis.
• Targeting G. morbillorum's invasion factors or secreted enzymes offers promising therapeutic avenues for CRC intervention.