Homo sapiens Raw sequence reads. Homo sapiens

SIN3A, a scaffold protein known to regulate diverse biological processes, has regulatory functions in tumor biology. We found that specific disruption of the PAH2 domain of SIN3A interaction with PF1 of TNBC cells profoundly inhibited invasion, migration and metastasis and promoted cellular senescence. ITGA6, ITGB1 and proteins linked to their downstream activity were downregulated. Genome wide transcriptomic analysis showed downregulation of multiple invasion related genes. Tumor growth and lung metastasis of human and mouse TNBC cells implanted in mice were markedly decreased. Overall, these data demonstrate a mechanism whereby invasion and metastasis of TNBC can be suppressed by inhibiting SIN3A and PF1 interaction and enhancing KLF9 mediated suppression of ITGA6 and ITGB1.