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Review
. 2022 Nov 7;10(11):2834.
doi: 10.3390/biomedicines10112834.

Emerging Role of YAP and the Hippo Pathway in Prostate Cancer

Filippos Koinis  1   2 , Evangelia Chantzara  1 , Michael Samarinas  3 , Anastasia Xagara  2 , Zisis Kratiras  4 , Vasiliki Leontopoulou  1 , Athanasios Kotsakis  1   2
Affiliations
Review

Emerging Role of YAP and the Hippo Pathway in Prostate Cancer

Filippos Koinis et al. Biomedicines. .

Abstract

The Hippo pathway regulates and contributes to several hallmarks of prostate cancer (PCa). Although the elucidation of YAP function in PCa is in its infancy, emerging studies have shed light on the role of aberrant Hippo pathway signaling in PCa development and progression. YAP overexpression and nuclear localization has been linked to poor prognosis and resistance to treatment, highlighting a therapeutic potential that may suggest innovative strategies to treat cancer. This review aimed to summarize available data on the biological function of the dysregulated Hippo pathway in PCa and identify knowledge gaps that need to be addressed for optimizing the development of YAP-targeted treatment strategies in patients likely to benefit.

Keywords: Hippo pathway; YAP; YAP/TAZ signaling; prostate cancer; prostate cancer hallmarks.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hippo YAP/TAZ signaling pathway in early PCa. When the Hippo pathway is switched ON, phosphorylation of Mst1 and Lats1 by Merlin and MAPK leads to phosphorylation of YAP/TAZ that forms a complex with 14–3–3 protein in the cytoplasm. VGLL4 binds to TEAD binding promoters thus, blocking the expression of genes important for proliferation, migration and tumorigenesis. In the OFF condition, in early prostate tumor cells, Lats1/2 is dephosphorylated due to various mechanisms such as degradation of Mst1/2 by Hsp27, complex formation of Lats1/2 with Par3 and Merlin and dissociation of Lats1/2 and KIBRA complex by Par3. Due to blocking of physiological kinase cascade of the Hippo pathway, unphosphorylated YAP/TAZ enters the nucleus and act as co-regulator of TEAD transcription factors leading to expression of target genes.
Figure 2
Figure 2
YAP and the Hallmarks of Cancer.
See this image and copyright information in PMC

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