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

Jin-E Liang; Bo-Wen Bao; Xue-Hua He; Wen-Qing Lu; Yang Liu; Jin Wang; Xiu-Juan Qu; Dong-Yang Li; Xiao-Fang Che

doi:10.1016/j.yexcr.2024.114331

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

Exp Cell Res. 2024 Nov 13:114331. doi: 10.1016/j.yexcr.2024.114331. Online ahead of print.

Authors

Jin-E Liang¹, Bo-Wen Bao², Xue-Hua He³, Wen-Qing Lu², Yang Liu⁴, Jin Wang², Xiu-Juan Qu², Dong-Yang Li⁵, Xiao-Fang Che⁶

Affiliations

¹ Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China; Clinical Cancer Research Center of Shenyang, the First Hospital of China Medical University, Shenyang 110001, China; Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, China.
² Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China; Clinical Cancer Research Center of Shenyang, the First Hospital of China Medical University, Shenyang 110001, China.
³ Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China; Clinical Cancer Research Center of Shenyang, the First Hospital of China Medical University, Shenyang 110001, China; Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, China.
⁴ Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China.
⁵ Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China; Clinical Cancer Research Center of Shenyang, the First Hospital of China Medical University, Shenyang 110001, China. Electronic address: [email protected].
⁶ Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China; Clinical Cancer Research Center of Shenyang, the First Hospital of China Medical University, Shenyang 110001, China. Electronic address: [email protected].

PMID: 39547354
DOI: 10.1016/j.yexcr.2024.114331

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: LOXL1; biomarker; cell cycle; gastric cancer; proliferation.