Mechanical cues shaping cancer cell-microbiota interaction dynamics in tumor progression

<h2>Summary</h2> Mechanical cues, such as shear stress and extracellular matrix (ECM) mechanics, substantially influence cancer cell-microbiota interactions within the tumor microenvironment (TME). This perspective examines how these mechanical cues regulate bacterial adhesion, invasion, and biofilm formation, subsequently altering cancer cell mechanics and tumor progression. We propose a mechano-microbial axis as a bidirectional framework where mechanical forces and ECM mechanics modulate bacterial uptake and spatial colonization, while microbiota reciprocally remodel the TME through metabolite-driven ECM degradation and immune modulation. Emerging therapeutic interventions, including bacterial adhesion inhibitors and biofilm-disrupting nanoparticles, highlight the potential to target this axis. However, key challenges persist in mapping bacterial dissemination patterns within tumors and elucidating single-cell mechano-microbial crosstalk. Integrating mechanical models with multi-omics approaches will bridge gaps, advancing mechanobiology-informed therapies that can dual-target microbiota dynamics and TME mechanics. By converging biomechanics, microbiology, and computational modeling, this field promises transformative strategies for targeted and effective cancer therapies.