Cross-Talk between p53 and Wnt Signaling in Cancer
Qiyun Xiao,
Johannes Werner,
Nachiyappan Venkatachalam,
Kim E. Boonekamp,
Matthias P. Ebert,
Tianzuo Zhan
Affiliations
Qiyun Xiao
Department of Medicine II, Mannheim University Hospital, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
Johannes Werner
Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ), and Department Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg University, D-69120 Heidelberg, Germany
Nachiyappan Venkatachalam
Department of Medicine II, Mannheim University Hospital, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
Kim E. Boonekamp
Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ), and Department Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg University, D-69120 Heidelberg, Germany
Matthias P. Ebert
Department of Medicine II, Mannheim University Hospital, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
Tianzuo Zhan
Department of Medicine II, Mannheim University Hospital, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
Targeting cancer hallmarks is a cardinal strategy to improve antineoplastic treatment. However, cross-talk between signaling pathways and key oncogenic processes frequently convey resistance to targeted therapies. The p53 and Wnt pathway play vital roles for the biology of many tumors, as they are critically involved in cancer onset and progression. Over recent decades, a high level of interaction between the two pathways has been revealed. Here, we provide a comprehensive overview of molecular interactions between the p53 and Wnt pathway discovered in cancer, including complex feedback loops and reciprocal transactivation. The mutational landscape of genes associated with p53 and Wnt signaling is described, including mutual exclusive and co-occurring genetic alterations. Finally, we summarize the functional consequences of this cross-talk for cancer phenotypes, such as invasiveness, metastasis or drug resistance, and discuss potential strategies to pharmacologically target the p53-Wnt interaction.