PRSS23-eIF4E-c-Myc axis promotes gastric tumorigenesis and progression.

IF 6.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Oncogene Pub Date : 2025-02-07 DOI:10.1038/s41388-025-03294-3

Xiaodong Zhou, Zixiang Guo, Yating Pan, Sicheng Yang, Runwei Yan

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引用次数: 0

Abstract

Gastric cancer is one of the most common malignant tumors. Our previous study showed that PRSS23 expression is increased in human gastric cancer tissues and PRSS23 knockdown inhibits gastric cancer cell growth. This current study aims to uncover the mechanism underlying PRSS23's involvement in gastric tumorigenesis and progression. We established that PRSS23 influences gastric cancer growth both in vitro and in vivo by modulating the eIF4E-c-Myc axis (eIF4E, p-eIF4E, 4EBP1, p-4EBP1, and c-Myc). Our investigation revealed that PRSS23 interacts with eIF4E via its trypsin domain, while eIF4E binds to PRSS23 through the amino acid residue S209, as confirmed by co-IP and immunofluorescence assays. Multiplexed immunofluorescence assay demonstrated a significant elevation of PRSS23 and p-4EBP1 levels in 232 paired gastric cancer tissues. Moreover, in 49 patients exhibiting relatively high PRSS23 expression, the levels of eIF4E-c-Myc axis-related proteins were increased. Importantly, higher PRSS23 expression correlated significantly with increased lymph node metastasis and advanced clinical staging, leading to poorer patient prognosis. These results highlight the role of upregulated PRSS23 in promoting gastric tumorigenesis and progression by activating the eIF4E-c-Myc axis, underscoring the PRSS23-eIF4E-c-Myc axis as a promising therapeutic target for gastric cancer.

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来源期刊

Oncogene 医学-生化与分子生物学

CiteScore

15.30

自引率

1.20%

发文量

404

审稿时长

1 months

期刊介绍： Oncogene is dedicated to advancing our understanding of cancer processes through the publication of exceptional research. The journal seeks to disseminate work that challenges conventional theories and contributes to establishing new paradigms in the etio-pathogenesis, diagnosis, treatment, or prevention of cancers. Emphasis is placed on research shedding light on processes driving metastatic spread and providing crucial insights into cancer biology beyond existing knowledge. Areas covered include the cellular and molecular biology of cancer, resistance to cancer therapies, and the development of improved approaches to enhance survival. Oncogene spans the spectrum of cancer biology, from fundamental and theoretical work to translational, applied, and clinical research, including early and late Phase clinical trials, particularly those with biologic and translational endpoints.