Obesity-mediated upregulation of the YAP/IL33 signaling axis promotes aggressiveness and induces an immunosuppressive tumor microenvironment in breast cancer

Jia Zih Dai, Ching Chieh Yang, Pei Wei Shueng, Yen Ju Wang, Chen Shiuan Huang, Yi Chun Chao, Cheng Hsun Chen, Cheng Wei Lin

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Obesity is a well-known risk factor for breast cancer formation and is associated with elevated mortality and a poor prognosis. An obesity-mediated inflammatory microenvironment is conducive to the malignant progression of tumors. However, the detailed molecular mechanism is still needed to be clarified. Herein, we identified that breast cancer cells from mice with diet-induced obesity exhibited increased growth, invasiveness, and stemness capacities. A transcriptome analysis revealed that expressions of interleukin 33 (IL33) signaling pathway-related genes were elevated in obesity-associated breast cancer cells. Importantly, IL33 expression was significantly associated with the yes-associated protein (YAP) signature, and IL33 was transcriptionally regulated by YAP. Suppression of IL33 reduced tumor migration and invasion, while the addition of IL33 activated nuclear factor (NF)-κB signaling and revived tumor mobility in YAP-silenced cells. Furthermore, suppression of YAP attenuated IL33 expression which was accompanied by relief of obesity-mediated immunosuppression. Clinical analyses showed that IL33 expression was markedly associated with macrophage and regulatory T cell infiltration. These findings reveal a crucial role of the YAP/IL33 axis in promoting aggressiveness and immunosuppression of obesity-associated breast cancer progression.

Original languageEnglish
Pages (from-to)992-1005
Number of pages14
JournalJournal of Cellular Physiology
Volume238
Issue number5
DOIs
Publication statusAccepted/In press - 2023

Keywords

  • breast cancer
  • immunosuppression
  • interleukin 33
  • obesity
  • yes-associated protein

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Obesity-mediated upregulation of the YAP/IL33 signaling axis promotes aggressiveness and induces an immunosuppressive tumor microenvironment in breast cancer'. Together they form a unique fingerprint.

Cite this