PPP1r18 promotes tumor progression in esophageal squamous cell carcinoma by regulating the calcineurin-mediated ERK pathway.

IF 3.3 3区医学 Q2 ONCOLOGY Carcinogenesis Pub Date : 2024-09-11 DOI:10.1093/carcin/bgae028

Changhao Ren, Linfeng Wu, Shaoyuan Zhang, Kangwei Qi, Yifei Zhang, Jiacheng Xu, Yuanyuan Ruan, Mingxiang Feng

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Abstract

Esophageal cancer is one of the most common malignant tumors, and the 5-year overall survival rate is only 20%. Esophageal squamous cell carcinoma (ESCC) is the primary histological type of esophageal carcinoma in China. Protein phosphatase 1 regulatory subunit 18 (PPP1r18) is one of the actin-regulatory proteins and is able to bind to protein phosphatase 1 catalytic subunit alpha (PPP1CA). Yet, little is known about the role of PPP1r18 in ESCC. This study aimed to elucidate the biological functions of PPP1r18 in the ESCC progression. Clinical samples first confirmed that PPP1r18 expression was upregulated in ESCC, and PPP1r18 was correlated with tumor invasion depth, lymph node metastasis, distant metastasis and reduced overall survival. We then observed that PPP1r18 overexpression enhanced cell proliferation in vitro and in vivo. Mechanistically, PPP1r18 regulated tumor progression of ESCC through activating the calcineurin-mediated ERK pathway, rather than binding to PPP1CA. Collectively, our results suggest that PPP1r18 promotes ESCC progression by regulating the calcineurin-mediated ERK pathway. PPP1r18 might be a potential target for the diagnosis and treatment of ESCC.

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PPP1r18 通过调节钙神经蛋白介导的 ERK 通路促进食管鳞状细胞癌的肿瘤进展。

食管癌是最常见的恶性肿瘤之一，5年总生存率仅为20%。食管鳞状细胞癌（ESCC）是中国食管癌的主要组织学类型。蛋白磷酸酶1调节亚基18（PPP1r18）是肌动蛋白调节蛋白之一，能与蛋白磷酸酶1催化亚基α（PPP1CA）结合。然而，人们对 PPP1r18 在食管鳞状细胞癌（ESCC）中的作用知之甚少。本研究旨在阐明PPP1r18在ESCC进展过程中的生物学功能。临床样本首先证实，PPP1r18在ESCC中表达上调，且PPP1r18与肿瘤侵袭深度、淋巴结转移、远处转移和总生存率降低相关。我们随后观察到，PPP1r18 的过表达增强了体外和体内的细胞增殖。从机理上讲，PPP1r18 是通过激活钙神经蛋白介导的 ERK 通路而不是与 PPP1CA 结合来调控 ESCC 的肿瘤进展的。总之，我们的研究结果表明，PPP1r18通过调节钙神经蛋白介导的ERK通路来促进ESCC的进展。PPP1r18可能是诊断和治疗ESCC的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Carcinogenesis 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

1 months

期刊介绍： Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).