LGR5 promotes invasion and migration by regulating YAP activity in hypopharyngeal squamous cell carcinoma cells under inflammatory condition

PLoS One. 2022 Oct 26;17(10):e0275679. doi: 10.1371/journal.pone.0275679. eCollection 2022.

Abstract

High leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) expression caused by an inflammatory condition was reported to promote tumor proliferation and the epithelial-mesenchymal transition (EMT) in various malignant tumors, but those effects have not been studied in hypopharyngeal squamous cell carcinoma (HSCC) and the molecular mechanism remains unclear. This study was aimed to determine whether YAP/TAZ is involved in the regulation of LGR5 expression in the inflammatory condition. Human hypopharyngeal carcinoma FaDu cells were stimulated with inflammatory medium. The cell invasion ability were evaluated through wound healing assay and transwell invasion assay. The expression levels of EMT-related proteins, LGR5, and p-YAP were detected by real time PCR, western blotting, and immunofluorescence. The results showed that LGR5 expression and the EMT process were significantly enhanced under inflammatory condition. The expression of EMT-related proteins was up-regulated, while that of p-YAP was decreased. After inhibiting the high LGR5 expression with short interfering RNA, the expression of EMT-related proteins was also down-regulated, while that of p-YAP was significantly increased. The use of verteporfin (VP), an inhibitor of YAP activity that promotes YAP phosphorylation, did not affect LGR5 expression. In conclusion, we suggest that the inflammatory condition leads to high LGR5 expression, which up-regulating the expression of EMT-related proteins by inhibiting the YAP phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition* / genetics
  • Head and Neck Neoplasms*
  • Humans
  • Leucine
  • Neoplastic Processes
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Squamous Cell Carcinoma of Head and Neck
  • Verteporfin / pharmacology

Substances

  • Leucine
  • LGR5 protein, human
  • Receptors, G-Protein-Coupled
  • RNA, Small Interfering
  • Verteporfin
  • YY1AP1 protein, human

Grants and funding

This study was supported by grants from Jilin Provincial Science& Technology Development (Grant No. 20200201493JC). 1. Initials of the authors who received each award: PW 2. Grant No. 20200201493JC 3. The full name of each funder: Jilin Provincial Science& Technology Development 4. URL of each funder website: http://kjt.jl.gov.cn/ 5. Did the sponsors or funders play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript?: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.