Migration and invasion inhibitory protein (MIIP) has been identified as a tumor suppressor in various cancer types. Although MIIP is reported to exert tumor suppressive functions by repressing proliferation and metastasis of cancer cells, the detailed mechanism is poorly understood. In the present study, we found MIIP is a favorable indicator of prognosis in triple-negative breast cancer. MIIP could inhibit tumor angiogenesis, proliferation, and metastasis of triple-negative breast cancer cells in vivo and in vitro. Mechanistically, MIIP directly interacted with ITGB3 and suppressed its downstream signaling. As a result, β-catenin was reduced due to elevated ubiquitin-mediated degradation, leading to downregulated VEGFA production and epithelial mesenchymal transition. More importantly, we found RGD motif is essential for MIIP binding with ITGB3 and executing efficient tumor-suppressing effect. Our findings unravel a novel mechanism by which MIIP suppresses tumorigenesis in triple-negative breast cancer, and MIIP is thus a promising molecular biomarker or therapeutic target for the disease.

Colorectal cancer (CRC) is one of the most common cancers worldwide and the consumption of a high-calorie diet is one of its risk factors. Calorie restriction (CR) slows tumor growth in a variety of cancers, including colorectal cancer; however, the mechanism behind this remains unknown. In the present study, CR effectively reduced the tumor volume and weight in a xenograft BALB/c male nude mouse model. In addition, tumor immunohistochemistry revealed that the CR group had significantly higher expression of Bax (P<0.001) and significantly lower levels of Bcl2 (P<0.0001) and Ki67 (P<0.001) compared with control group. Furthermore, data from 16S ribosomal (r)RNA sequencing implied that CR was able to reprogram the microbiota structure, characterized by increased Lactobacillus constituent ratio (P<0.05), with amelioration of microbial dysbiosis caused by CRC. Further receiver operating characteristic curves demonstrated that the bacteria Bacteroides [area under the curve (AUC)=0.800], Lactobacillus (AUC= 0.760) and Roseburia (AUC= 0.720) served key roles in suppression of CRC in the mouse model. The functional prediction of intestinal flora indicated 'cyanoamino acid metabolism' (P<0.01), 'replication initiation protein REP (rolling circle plasmid replication)' (P<0.01), 'tRNA G10 N-methylase Trm11' (P<0.01) and 'uncharacterized protein with cyclophilin fold, contains DUF369 domain' (P<0.05) were downregulated in CR group. These findings implied that CR suppressed CRC in mice and altered the gut microbiota.