Low-intensity vibration (LIV) cellular mechanotherapy reprograms tumor transcriptomes to suppress cancer-promoting inflammation
LIV is a non-pharmacological intervention for multiple pathologies, most notably pain, yet its potential in oncology remains unexplored due to poorly understood mechanotransduction pathways. Its therapeutic efficacy depends on precise dosing parameters - frequency, amplitude, and duration; suboptimal application, whether excessive or insufficient, risks exacerbating symptoms or rendering treatment ineffective. In a breast cancer-immune cell co-culture model, a 15-min regimen of 90-Hz, 0.43-g LIV attenuates protumorigenic crosstalk by suppressing proinflammatory cytokines and reprogramming malignant cells into a transient metastasis-incompetent "benignant" state that retains oncogenic markers but loses invasive capacity. Our results reveal LIV as a non-drug inhibitor of IFN{gamma} and CXCL12{beta} - silencing IFN{gamma} impairs inflammatory bursts, while silencing CXCL12{beta} starves the CXCR4/CXCR7 axis, depriving tumor cells of motility cues. LIV enforces a genome-wide transcriptional brake, upregulating tumor-suppressive miRNAs (hsa-miR-141, hsa-miR-122) while downregulating protumorigenic miRNAs (hsa-miR-105-5p, hsa-miR-181a-5p). This work repositions LIV as a non-drug modality for coordinately targeting multiple cancer hallmarks. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/716739v1_ufig1.gif" ALT="Figure 1"> View larger version (80K): org.highwire.dtl.DTLVardef@1100863org.highwire.dtl.DTLVardef@196bcf4org.highwire.dtl.DTLVardef@14f3903org.highwire.dtl.DTLVardef@2802fd_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_ST_ABSDosing PrecisionC_ST_ABSLIV mechanotherapy has an optimal therapeutic window. Too little is ineffective, while too much can exacerbate symptoms. This mirrors the pharmacokinetic language of classical pharmacology. The "Benignant" ConceptA 15-min regimen of 90-Hz, 0.43-g LIV attenuates protumorigenic crosstalk by suppressing proinflammatory cytokines and reprogramming malignant cells into a transient, metastasis-incompetent benignant state defined by mechanical constraint rather than pharmacological intervention. Dual Cytokine SilencingLIV acts as a non-pharmaco-logical inhibitor of IFN{gamma} and CXCL12{beta}. IFN{gamma} is a double-edged sword in cancer (pro-immunity vs. exhaustion), and CXCL12{beta} is the specific isoform implicated in metastasis. Targeting both simultaneously addresses immune crosstalk and chemotaxis. In briefMeena et al. demonstrate that the efficacy of LIV hinges on optimal dosing parameters. When applied correctly, it functions as a non-drug modality to target multiple oncogenic and inflammatory pathways. At the molecular level, LIV drives global transcriptional repression via miRNA regulation, increasing tumor-suppressive miRNAs (hsa-miR-141, hsa-miR-122) and decreasing protumorigenic miRNAs (hsa-miR-105-5p, hsa-miR-181a-5p).