Proteomic Analysis of Caco‑2 Cells Disrupted by EcN 1917-Derived OMVs Reveals Molecular Information on Bacteria-Mediated Cancer Cell Migration

Escherichia coli Nissle 1917 (EcN 1917)
exhibits
distinct tumor-targeting activity, and early studies demonstrated
that outer membrane vesicles (OMVs) mediate bacteria–host interactions.
To decipher the molecular mechanism underlying the interaction between
EcN 1917 and host cells via OMV-mediated communication, we investigated
the phenotypic changes in Caco-2 cells perturbed by EcN 1917-derived
OMVs and constructed proteomic maps of the EcN 1917-derived OMV components
and OMV-perturbed host cells. Our findings revealed that the size
of the EcN 1917-derived OMV proteome increased 4-fold. Treatment with
EcN 1917-derived OMVs altered the proteomic and phosphoproteomic profiles
of host cells. Importantly, for the first time, we found that treatment
with EcN 1917-derived OMVs inhibited cancer cell migration by suppressing
the expression of ANXA9. In addition, phosphoproteomic data suggested
that the ErbB pathway may be involved in OMV-mediated cell migration.
Taken together, our study provides valuable data for further investigations
of OMV-mediated bacteria–host interactions and offers great
insights into the underlying mechanism of probiotic-assisted colorectal
cancer therapy.