» Articles » PMID: 39123485

Emerging Role of Hippo-YAP (Yes-Associated Protein)/TAZ (Transcriptional Coactivator with PDZ-Binding Motif) Pathway Dysregulation in Renal Cell Carcinoma Progression

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2024 Aug 10
PMID 39123485
Authors
Affiliations
Soon will be listed here.
Abstract

Although Hippo-YAP/TAZ pathway involvement has been extensively studied in the development of certain cancers, the involvement of this cascade in kidney cancer progression is not well-established and, therefore, will be the focus of this review. Renal cell carcinoma (RCC), the most prevalent kidney tumor subtype, has a poor prognosis and a high mortality rate. Core Hippo signaling inactivation (e.g., LATS kinases) leads to the nuclear translocation of YAP/TAZ where they bind to co-transcriptional factors such as TEAD promoting transcription of genes which initiates various fibrotic and neoplastic diseases. Loss of expression of LATS1/2 kinase and activation of YAP/TAZ correlates with poor survival in RCC patients. Renal-specific ablation of LATS1 in mice leads to the spontaneous development of several subtypes of RCC in a YAP/TAZ-dependent manner. Genetic and pharmacological inactivation of YAP/TAZ reverses the oncogenic potential in LATS1-deficient mice, highlighting the therapeutic benefit of network targeting in RCC. Here, we explore the unique upstream controls and downstream consequences of the Hippo-YAP/TAZ pathway deregulation in renal cancer. This review critically evaluates the current literature on the role of the Hippo pathway in RCC progression and highlights the recent scientific evidence designating YAP/TAZ as novel therapeutic targets against kidney cancer.

References
1.
Anorga S, Overstreet J, Falke L, Tang J, Goldschmeding R, Higgins P . Deregulation of Hippo-TAZ pathway during renal injury confers a fibrotic maladaptive phenotype. FASEB J. 2018; 32(5):2644-2657. PMC: 5901380. DOI: 10.1096/fj.201700722R. View

2.
Philips G, Atkins M . New agents and new targets for renal cell carcinoma. Am Soc Clin Oncol Educ Book. 2014; :e222-7. DOI: 10.14694/EdBook_AM.2014.34.e222. View

3.
Argani P, Reuter V, Eble J, Vlatkovic L, Yaskiv O, Swanson D . Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma (BHP RCC): A Distinctive Neoplasm Associated With Somatic NF2 Mutations. Am J Surg Pathol. 2020; 44(7):901-916. PMC: 7350624. DOI: 10.1097/PAS.0000000000001467. View

4.
Kumar B, Ahmad R, Giannico G, Zent R, Talmon G, Harris R . Claudin-2 inhibits renal clear cell carcinoma progression by inhibiting YAP-activation. J Exp Clin Cancer Res. 2021; 40(1):77. PMC: 7901196. DOI: 10.1186/s13046-021-01870-5. View

5.
Gupta K, Miller J, Li J, Russell M, Charbonneau C . Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev. 2008; 34(3):193-205. DOI: 10.1016/j.ctrv.2007.12.001. View