SOX10+ expression correlates with m

SOX10+ expression correlates with mammary tumor cell stateplasticityBecause SOX10 overexpression can also induce motility andmammary cell delamination in 3D culture (Dravis et al., 2015),we determined whether SOX10high cells also locally invade inmouse tumor models in vivo. Strikingly, significant numbers ofSOX10high cells in PY230 tumors were found outside the primarytumor margin and in close proximity to tumor vasculature (Figure 5G and Video S1).We examined the TCGA database to determine whetherSOX10 is similarly linked to EMT and dedifferentiation in humanbreast cancer. We generated a rank-order list of human genesbased on the correlation of their expression with SOX10 expression across a panel of human breast tumors. Many EMT-relatedgenes positively correlated with SOX10 expression, whereasmany epithelial/differentiation-related genes negatively correlated with SOX10 expression (Figures 5H and S5E). Consistentwith these data, SOX10 expression in malignant tissue correlated with undetectable or low expression of K14 and K8,compared with adjacent benign mammary tissue on the section, in the same human ERPRHER2 breast cancer sample (Figures 3G and S4C). Clear expression of the mesenchymal markerVIM could also be detected in many of the SOX10+ tumor cells(Figure 5I).Taken together, these data establish a link between SOX10and partial EMT/dedifferentiation in breast cancer. The datafurther indicate links between SOX10 and local invasion andmetastasis, critical features of cancer-associated mortality.