The article by Paul Polakis provides an overview of the role of Wnt signaling in cancer. It begins with the historical discovery that Wnt signaling pathway activation can lead to malignant transformation in mouse mammary tissue, highlighting its central role in cancer biology. The author reviews genetic mutations affecting Wnt pathway components and epigenetic mechanisms that alter gene expression related to Wnt signaling. Key mutations include those in APC, Axin, β-catenin, and TCF transcription factors, which are frequently found in various cancers. Epigenetic modifications, such as DNA methylation and chromatin modifications, also play a significant role in regulating Wnt signaling. The article further discusses the cooperation between Wnt signaling and other signaling pathways, such as prostaglandin signaling, and the androgen receptor, which can enhance or synergize with Wnt signaling to promote tumor growth. Experimental evidence is presented to support the therapeutic inhibition of Wnt signaling in cancer, including the use of dominant negative TCF4, β-catenin knockdown, and Wnt receptor inhibitors. The article concludes by emphasizing the importance of Wnt signaling in human tumor progression and the potential for developing targeted therapies to interfere with this pathway.The article by Paul Polakis provides an overview of the role of Wnt signaling in cancer. It begins with the historical discovery that Wnt signaling pathway activation can lead to malignant transformation in mouse mammary tissue, highlighting its central role in cancer biology. The author reviews genetic mutations affecting Wnt pathway components and epigenetic mechanisms that alter gene expression related to Wnt signaling. Key mutations include those in APC, Axin, β-catenin, and TCF transcription factors, which are frequently found in various cancers. Epigenetic modifications, such as DNA methylation and chromatin modifications, also play a significant role in regulating Wnt signaling. The article further discusses the cooperation between Wnt signaling and other signaling pathways, such as prostaglandin signaling, and the androgen receptor, which can enhance or synergize with Wnt signaling to promote tumor growth. Experimental evidence is presented to support the therapeutic inhibition of Wnt signaling in cancer, including the use of dominant negative TCF4, β-catenin knockdown, and Wnt receptor inhibitors. The article concludes by emphasizing the importance of Wnt signaling in human tumor progression and the potential for developing targeted therapies to interfere with this pathway.