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

• Published in: Experimental cell research 2024-12, Vol.443 (2), p.114331, Article 114331
• Main Authors: Liang, Jin-e, Bao, Bo-wen, He, Xue-hua, Lu, Wen-qing, Liu, Yang, Wang, Jin, Qu, Xiu-juan, Li, Dong-yang, Che, Xiao-fang
• Format: Article
• Language: English
• Subjects: Biomarker; Cell cycle; Gastric cancer; LOXL1; Proliferation
• ISSN: 0014-4827; 1090-2422; 1090-2422
• DOI: 10.1016/j.yexcr.2024.114331

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. •LOXL1 is the only independent prognostic risk factor in GC among all of LOX family members.•We construct a nomogram model based on LOXL1 expression.•LOXL1 leads to poor prognosis by promoting GC cell proliferation via WNT/β-catenin/cyclin D1 pathway.