Voglstaetter M, et al. - Researchers displayed a first study on the expression and function of Tspan8 (plays a functional role in many cancer types including pancreatic, colorectal, esophagus carcinoma, and melanoma) in breast cancer. Biopsies from breast cancer cases and normal breast samples were collected from subjects who underwent plastic surgery. Tspan8 protein was observed in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. Tspan8⁺ tumors created multiple liver and spleen metastases, while Tspan8⁻ tumors showed a significantly reduced ability to metastasize, symbolizing the role of Tspan8 in metastases, in a syngeneic rat breast cancer model. Tspan8 could mediate the up-regulation of E-cadherin and down-regulation of Twist, p120-catenin, and β-catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal-epithelial transition. Moreover, enhanced cell-cell adhesion, diminished motility, and decreased sensitivity to irradiation were demonstrated by Tspan8+ cells. Tspan8 mediated a several-fold rise in extracellular vesicle (EV) numbers in cell culture and the circulation of tumor-bearing animals as a regulator of the content and function of EVs. In these EVs, raised protein levels of E-cadherin and p120-catenin were noted. Besides, Tspan8 and p120-catenin were co-immunoprecipitated, which symbolized that they may communicate with each other. Hence, the conclusions exhibited the presence of Tspan8 in breast cancer primary lesion and metastases and symbolized its role in breast cancer as a regulator of cell behavior and EV release.