Intratumoral bacterium Enterocloster bolteae promotes hepatocellular carcinoma progression by directly binding tumor cells.

E. bolteae is enriched in the feces of HCC patients and is associated with poor prognosis.

• E. bolteae abundance was elevated in fecal samples from HCC patients compared to controls.
• Higher intratumoral or fecal E. bolteae levels correlated with worse clinical outcomes in HCC patients.
• The association with poor prognosis was identified through clinical cohort analysis.

E. bolteae disrupts intestinal barrier integrity and translocates to the liver.

• E. bolteae was shown to compromise gut barrier function, enabling bacterial translocation through the gut-liver axis.
• Translocated bacteria were detected in liver tumor tissue.
• This translocation was demonstrated experimentally in the study's in vivo models.

E. bolteae promotes tumor cell proliferation in hepatocellular carcinoma.

• E. bolteae directly promoted HCC tumor cell proliferation in experimental models.
• The tumor-promoting effect was demonstrated both in vitro and in vivo.
• Blockade of the bacterial surface protein PbpT abrogated E. bolteae's role in promoting HCC progression.

E. bolteae's surface protein PbpT directly interacts with the tumor cell receptor desmoglein 1 (DSG1).

• PbpT is described as a 'penicillin-binding transpeptidase domain-containing protein' on the surface of E. bolteae.
• PbpT binds directly to DSG1 expressed on HCC tumor cells.
• This direct protein-receptor interaction facilitates bacterial adhesion to tumor cells.
• The interaction was identified mechanistically as a key step in E. bolteae's tumor-promoting activity.

The PbpT-DSG1 interaction attenuates DSG1's tumor-suppressive function in HCC cells.

• DSG1 was identified as having a tumor-suppressive role in HCC.
• Binding of E. bolteae's PbpT to DSG1 attenuated this tumor-suppressive function.
• Loss of DSG1's suppressive activity upon bacterial binding contributes to HCC progression.

The PbpT-DSG1 interaction activates the MAPK signaling pathway to accelerate HCC progression.

• Binding of PbpT to DSG1 activated the mitogen-activated protein kinase (MAPK) signaling pathway.
• MAPK pathway activation was identified as a downstream consequence of the PbpT-DSG1 interaction.
• The PbpT-DSG1-MAPK axis was described as 'a critical driver of HCC progression.'

Blockade of PbpT abrogates E. bolteae attachment to tumor cells and its tumor-promoting effects.

• Targeting PbpT prevented E. bolteae from adhering to HCC tumor cells.
• PbpT blockade abolished the tumor-promoting activity of E. bolteae.
• Targeting PbpT was proposed as 'a promising therapeutic strategy for HCC.'