Department of Medicine II, Mannheim University Hospital, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
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.
Biomolecules. 2022 Mar 15;12(3):453. doi: 10.3390/biom12030453.
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.
针对癌症特征是改善抗肿瘤治疗的主要策略。然而，信号通路之间的串扰和关键致癌过程经常导致对靶向治疗的耐药性。p53 和 Wnt 通路对于许多肿瘤的生物学特性至关重要，因为它们在癌症的发生和进展中起着关键作用。在过去的几十年中，已经揭示了这两条通路之间存在高度的相互作用。在这里，我们全面概述了在癌症中发现的 p53 和 Wnt 通路之间的分子相互作用，包括复杂的反馈环和相互转录激活。描述了与 p53 和 Wnt 信号相关的基因的突变景观，包括相互排斥和共同发生的遗传改变。最后，我们总结了这种串扰对癌症表型的功能后果，例如侵袭性、转移或耐药性，并讨论了药理学靶向 p53-Wnt 相互作用的潜在策略。
