Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer

Tumor-resident intracellular microbiota is an emerging tumor component that has been documented for a variety of cancer types with unclear biological functions. Here, we explored the functional significance of these intratumor bacteria, primarily using a murine spontaneous breast-tumor model MMTV-PyMT. We found that depletion of intratumor bacteria significantly reduced lung metastasis without affecting primary tumor growth. During metastatic colonization, intratumor bacteria carried by circulating tumor cells promoted host-cell survival by enhancing resistance to fluid shear stress by reorganizing actin cytoskeleton. We further showed that intratumor administration of selected bacteria strains isolated from tumor-resident microbiota promoted metastasis in two murine tumor models with significantly different levels of metastasis potential. Our findings suggest that tumor-resident microbiota, albeit at low biomass, play an important role in promoting cancer metastasis, intervention of which might therefore be worth exploring for advancing oncology care. [Display omitted] •Conserved intracellular bacterial profile is detected in murine and human breast cancer•Perturbation of intracellular bacteria reduces metastasis but not primary tumor growth•Intracellular bacteria reorganize actin cytoskeleton in circulating tumor cells (CTCs)•Intracellular bacteria promote CTC survival by enhancing resistance to mechanical stress Tumor-resident intracellular bacteria enhance survival of circulating tumor cells by cytoskeleton reorganization. They promote metastasis but are not required for primary tumor growth in a murine breast cancer model.