Wnt signaling is involved in the regulation of cancer stem cells (CSCs); however, the molecular mechanism involved is still obscure. SFRP1, a Wnt inhibitor, is downregulated in various human cancers; however, its role in tumor initiation and CSC regulation remains unexplored. Here, we used a skin carcinogenesis model, which showed early tumor initiation in Sfrp1^−/− (Sfrp1 knockout) mice and increased tumorigenic potential of Sfrp1^−/− CSCs. Expression profiling on Sfrp1^−/− CSCs showed upregulation of genes involved in epithelial to mesenchymal transition, stemness, proliferation, and metastasis. Further, SOX-2 and SFRP1 expression was validated in human skin cutaneous squamous cell carcinoma, head and neck squamous cell carcinoma, and breast cancer. The data showed downregulation of SFRP1 and upregulation of SOX-2, establishing their inverse correlation. Importantly, we broadly uncover an inverse correlation of SFRP1 and SOX-2 in epithelial cancers that may be used as a potential prognostic marker in the management of cancer.

Wnt信号传导参与癌症干细胞（CSCs）的调控。但是，所涉及的分子机制仍然不清楚。SFRP1，Wnt抑制剂，被下调在各种人类癌症; 然而，其在肿瘤起始和CSC调节中的作用尚待探索。在这里，我们使用了皮肤癌变模型，该模型显示了Sfrp1 ^-/-（Sfrp1基因敲除）小鼠的早期肿瘤萌发和Sfrp1 ^-/- CSCs的致瘤潜力增加。Sfrp1 ^-/- CSC上的表达谱显示上皮到间充质转化，干，增殖和转移相关基因的上调。此外，SOX-2和SFRP1表达在人皮肤皮肤鳞状细胞癌，头颈鳞状细胞癌和乳腺癌中得到验证。数据显示的下调SFRP1和上调的SOX-2 ，建立其逆相关。重要的是，我们广泛地揭示了上皮癌中SFRP1和SOX-2的负相关，可以用作癌症预后的潜在标志。