LOXL1 promotes gastric cancer progression by β-catenin-cyclinD mediated proliferation

Exp Cell Res. 2024 Dec 1;443(2):114331. doi: 10.1016/j.yexcr.2024.114331. Epub 2024 Nov 13.

Abstract

Although much progress has been made in chemotherapy or target therapy for advanced gastric cancer, the prognosis is still poor. It is necessary to screen biomarkers for early diagnosis and prognosis prediction. However, the prognostic value of LOX family in gastric cancer and the underlying molecular mechanisms for promoting the progression of gastric cancer remains unclear. Among five members of LOX family, LOXL1 was the unique independent prognostic risk factor. The nomogram established based on the expression of LOXL1 and other clinical parameters could predict the overall survival rate of gastric cancer. Knockdown (KD) of LOXL1 decreased cell proliferation and led to G1 phase arrest in gastric cells. According to GSEA analysis that LOXL1 was positively correlated with the WNT signaling pathway, in vitro experiment proved that LOXL1-KD reduced the phosphorylation level of β-catenin and the expression of the downstream G1 phase checkpoint CCND1. In conclusion, LOXL1 has been identified as a potential risk prognostic biomarker for gastric cancer by promoting gastric cancer proliferation via WNT/β-catenin/cyclinD1 pathway.

Keywords: Biomarker; Cell cycle; Gastric cancer; LOXL1; Proliferation.

MeSH terms

  • Amino Acid Oxidoreductases* / genetics
  • Amino Acid Oxidoreductases* / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation* / genetics
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology
  • Wnt Signaling Pathway* / genetics
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • beta Catenin
  • LOXL1 protein, human
  • Amino Acid Oxidoreductases
  • Cyclin D1
  • CTNNB1 protein, human
  • CCND1 protein, human
  • Biomarkers, Tumor