Hippo signaling modulation and its biological implications in urological malignancies

Mol Aspects Med. 2024 Aug:98:101280. doi: 10.1016/j.mam.2024.101280. Epub 2024 Jun 12.

Abstract

Although cancer diagnosis and treatment have rapidly advanced in recent decades, urological malignancies, which have high morbidity and mortality rates, are among the most difficult diseases to treat. The Hippo signaling is an evolutionarily conserved pathway in organ size control and tissue homeostasis maintenance. Its downstream effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are key modulators of numerous physiological and pathological processes. Recent work clearly indicates that Hippo signaling is frequently altered in human urological malignancies. In this review, we discuss the disparate viewpoints on the upstream regulators of YAP/TAZ and their downstream targets and systematically summarize the biological implications. More importantly, we highlight the molecular mechanisms involved in Hippo-YAP signaling to improve our understanding of its role in every stage of prostate cancer, bladder cancer and kidney cancer progression. A better understanding of the biological outcomes of YAP/TAZ modulation will contribute to the establishment of future therapeutic approaches.

Keywords: Bladder cancer; Hippo signaling; Kidney cancer; Prostate cancer; Transcriptional regulation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Gene Expression Regulation, Neoplastic
  • Hippo Signaling Pathway*
  • Humans
  • Male
  • Protein Serine-Threonine Kinases* / metabolism
  • Signal Transduction*
  • Transcription Factors* / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins / metabolism
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Urologic Neoplasms / etiology
  • Urologic Neoplasms / metabolism
  • Urologic Neoplasms / pathology
  • YAP-Signaling Proteins / metabolism

Substances

  • Protein Serine-Threonine Kinases
  • Transcription Factors
  • YAP-Signaling Proteins
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Adaptor Proteins, Signal Transducing
  • YAP1 protein, human
  • WWTR1 protein, human