Mutant p53 Protein and the Hippo Transducers YAP and TAZ: A Critical Oncogenic Node in Human Cancers

Area of Science:

• Oncology
• Molecular Biology
• Cellular Biology

Background:

• The p53 protein is a critical tumor suppressor regulating cellular homeostasis, earning it the nickname "guardian of the genome."
• Mutations in the TP53 gene can lead to both loss-of-function and gain-of-function alterations, contributing to cancer development.
• The Hippo pathway is essential for development and regeneration but can drive cancer when deregulated.

Purpose of the Study:

• To explore the intricate relationship between the p53 and Hippo pathways in cancer.
• To investigate how p53 status influences the Hippo pathway's function, potentially shifting it from tumor suppression to oncogenesis.
• To detail the mechanisms by which mutant p53 interacts with Hippo pathway components.

Main Methods:

• This review synthesizes existing research on p53 and Hippo pathway interactions.
• It analyzes the literature concerning the oncogenic roles of specific protein complexes and activations.
• The discussion focuses on the functional consequences of mutant p53 in the context of Hippo pathway signaling.

Main Results:

• Mutant p53 can form oncogenic complexes with YAP, a key component of the Hippo pathway.
• Mutant p53 can mediate the oncogenic activation of TAZ, another critical Hippo pathway effector.
• The p53 status appears to dictate whether the Hippo pathway acts as a tumor suppressor or an oncogene.

Conclusions:

• The p53 protein's functional status significantly impacts the Hippo pathway's role in tumorigenesis.
• Mutant p53 can hijack the Hippo pathway, promoting cancer through interactions with YAP and TAZ.
• Understanding these pathway crosstalks is crucial for developing targeted cancer therapies.