A review: hippo signaling pathway promotes tumor invasion and metastasis by regulating target gene expression

J Cancer Res Clin Oncol. 2021 Jun;147(6):1569-1585. doi: 10.1007/s00432-021-03604-8. Epub 2021 Apr 17.

Abstract

Background: The Hippo pathway is widely considered to inhibit cell growth and play an important role in regulating the size of organs. However, recent studies have shown that abnormal regulation of the Hippo pathway can also affect tumor invasion and metastasis. Therefore, finding out how the Hippo pathway promotes tumor development by regulating the expression of target genes provides new ideas for future research on targeted drugs that inhibit tumor progression.

Methods: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched.

Results: The search strategy identified 1892 hits and 196 publications were finally included in this review. As the core molecule of the Hippo pathway, YAP/TAZ are usually highly expressed in tumors that undergo invasion and migration and are accompanied by abnormally strong nuclear metastasis. Through its interaction with nuclear transcription factors TEADs, it directly or indirectly regulates and the expressions of target genes related to tumor metastasis and invasion. These target genes can induce the formation of invasive pseudopodia in tumor cells, reduce intercellular adhesion, degrade extracellular matrix (ECM), and cause epithelial-mesenchymal transition (EMT), or indirectly promote through other signaling pathways, such as mitogen-activated protein kinases (MAPK), TGF/Smad, etc, which facilitate the invasion and metastasis of tumors.

Conclusion: This article mainly introduces the research progress of YAP/TAZ which are the core molecules of the Hippo pathway regulating related target genes to promote tumor invasion and metastasis. Focus on the target genes that affect tumor invasion and metastasis, providing the possibility for the selection of clinical drug treatment targets, to provide some help for a more in-depth study of tumor invasion and migration mechanism and the development of clinical drugs.

Keywords: Hippo pathway; Invasion and metastasis; Target gene; Tumor; YAP/TAZ.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Hippo Signaling Pathway
  • Humans
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Metastasis / genetics*
  • Protein Serine-Threonine Kinases / physiology*
  • Signal Transduction / genetics
  • Transcription Factors / genetics

Substances

  • Transcription Factors
  • Protein Serine-Threonine Kinases