A time for YAP1: Tumorigenesis, immunosuppression and targeted therapy

Masahiro Shibata, Kendall Ham, Mohammad Hoque

Research output: Contribution to journalReview article

Abstract

YAP1 is one of the most important effectors of the Hippo pathway and has crosstalk with other cancer promoting pathways. YAP1 contributes to cancer development in various ways that include promoting malignant phenotypes, expansion of cancer stem cells and drug resistance of cancer cells. Because pharmacologic or genetic inhibition of YAP1 suppresses tumor progression and increases the drug sensitivity, targeting YAP1 may open a fertile avenue for a novel therapeutic approach in relevant cancers. Recent enormous studies have established the efficacy of immunotherapy, and several immune checkpoint blockades are in clinical use or in the phase of development to treat various cancer types. Immunosuppression in the tumor microenvironment (TME) induced by cancer cells, immune cells and associated stromal cells promotes tumor progression and causes drug resistance. Accumulated evidences of scientific efforts from the last few years suggest that YAP1 influences macrophages, myeloid-derived suppressor cells and regulatory T-cells to facilitate immunosuppressive TME. Although the underlying mechanisms is not clearly discerned, it is evident that YAP1 activating pathways in different cellular components induce immunosuppressive TME. In this review, we summarize the evidences involved in the dual roles of YAP1 in cancer development and immunosuppression in the TME. We also discuss the possibility of YAP1 as a novel therapeutic target.

Original languageEnglish (US)
Pages (from-to)2133-2144
Number of pages12
JournalInternational Journal of Cancer
Volume143
Issue number9
DOIs
StatePublished - Nov 1 2018

Keywords

  • cancer development
  • immunosuppression
  • tumor microenvironment and targeted therapy
  • YAP1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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