Sox2 upregulation has been found in tumor-initiating cells or precursors of osteosarcomas,21 glioblastoma,22 lung and esophageal squamous cell carcinomas,23 and breast cancer.24 In our previous studies, we have shown that Sox2 is markedly upregulated in melanoma TRCs.2, 3 More recently, we have discovered an essential role of Sox2 in mediating efficient extravasation of melanoma TRCs via downregulating Cdc42 and thus F-actin in a zebrafish model.25 However, Sox2 may not be the only critical factor in various carcinomas as in many carcinomas there is no evidence that Sox2 is upregulated. The gene discussed is CDC42; the disease is osteosarcoma.