P4HA2通过激活EGFR/AKT/S6信号通路促进食管鳞癌细胞的增殖

doi:10.3969/j.issn.1004-616x.2023.02.002

癌变·畸变·突变 ›› 2023, Vol. 35 ›› Issue (2): 87-94,101.doi: 10.3969/j.issn.1004-616x.2023.02.002

• 论著 • 上一篇

P4HA2通过激活EGFR/AKT/S6信号通路促进食管鳞癌细胞的增殖

冯丹¹, 范志露¹, 王意浓¹, 李赛¹, 郭婧¹, 蔡岩¹, 张钰¹, 魏文强², 王明荣¹, 郝佳洁¹

1. 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 分子肿瘤学国家重点实验室, 北京 100021;
2. 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 流行病学中心, 北京 100021

收稿日期:2023-02-10 修回日期:2023-02-24 发布日期:2023-04-13
通讯作者: 王明荣;郝佳洁
作者简介:冯丹,E-mail：13509725440@163.com。
基金资助:
国家重点研发计划项目(2021YFC2501000)；国家自然科学基金项目(81972770)；中国医学科学院医学与健康科技创新工程项目(2021-1-I2M-018)

P4HA2 promotes proliferation of esophageal squamous carcinoma cells via activating the EGFR/AKT/S6 signaling pathway

FENG Dan¹, FAN Zhilu¹, WANG Yinong¹, LI Sai¹, GUO Jing¹, CAI Yan¹, ZHANG Yu¹, WEI Wenqiang², WANG Mingrong¹, HAO Jiajie¹

1. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021;
2. Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Received:2023-02-10 Revised:2023-02-24 Published:2023-04-13

摘要/Abstract

摘要： 目的：探讨P4HA2在食管鳞癌中的表达情况及作用机制。方法：利用基因表达综合数据库(GEO)的RNA表达谱数据及免疫组织化学染色和Western blot技术分析食管鳞癌组织及正常食管组织中P4HA2的mRNA和蛋白表达情况；通过细胞增殖实验、集落形成实验和裸鼠移植瘤实验，在体外和体内检测P4HA2对食管鳞癌细胞恶性表型的影响；利用Western blot检测P4HA2调控的下游通路及关键分子。结果：与正常食管组织相比，食管鳞癌组织中P4HA2的mRNA和蛋白水平均显著升高(P<0.01)；体外和体内实验结果显示，与对照组相比，敲降P4HA2可显著抑制食管鳞癌细胞的增殖、集落形成以及裸鼠移植瘤的生长(P<0.01)；分子水平检测表明，敲降P4HA2显著降低EGFR的蛋白水平，以及AKT和S6的磷酸化水平(P<0.05)；在食管鳞癌细胞中敲降P4HA2后回复EGFR的表达，AKT和S6的磷酸化水平以及细胞增殖和集落形成表型均得以恢复(P<0.01)。结论：P4HA2在食管鳞癌组织中高表达，且P4HA2通过激活EGFR/AKT/S6信号通路促进食管鳞癌细胞的增殖和肿瘤生长。

关键词: P4HA2, 食管鳞癌, 细胞增殖, EGFR/AKT/S6信号通路

Abstract: OBJECTIVE： To investigate expression and implication of P4HA2 in esophageal squamous cell carcinoma (ESCC). METHODS： Expressions of P4HA2 mRNA in ESCC tissues and normal esophageal tissues were analyzed by Gene Expression Omnibus (GEO) database. P4HA2 protein in ESCC and normal tissues were detected using Immunohistochemistry (IHC) and Western blot. Cell proliferation and colony formation assays were performed to analyze effects of P4HA2 on the malignant phenotypes of ESCC cells in vitro. Effects of P4HA2 on tumor growth were detected using the nude mouse xenograft model in vivo. Western blot was used to analyze changes in downstream pathways from knockdown of P4HA2. RESULTS：Expression levels of both the P4HA2 mRNA and protein were up-regulated in ESCC compared with the normal tissues (P<0.01). In vitro and in vivo results showed that P4HA2 silencing significantly inhibited the proliferation and colony formation of ESCC cells，as well as the growth of tumor xenografts (P<0.01). At the molecular level， P4HA2 knockdown down-regulated EGFR expression，and reduced the phosphorylation levels of AKT and S6 (P<0.05). Moreover，P4HA2 knockdown and over-expression of EGFR significantly restored the phosphorylation levels of AKT and S6 as well as cell proliferation and colony formation (P<0.01). CONCLUSION：P4HA2 was highly expressed in ESCC，and it might enhance cell proliferation and promote development of ESCC via activating the EGFR/AKT/S6 pathway.

Key words: P4HA2, esophageal squamous cell carcinoma, cell proliferation, EGFR/AKT/S6 signaling pathway

中图分类号:

R735.1

冯丹, 范志露, 王意浓, 李赛, 郭婧, 蔡岩, 张钰, 魏文强, 王明荣, 郝佳洁. P4HA2通过激活EGFR/AKT/S6信号通路促进食管鳞癌细胞的增殖[J]. 癌变·畸变·突变, 2023, 35(2): 87-94,101.

FENG Dan, FAN Zhilu, WANG Yinong, LI Sai, GUO Jing, CAI Yan, ZHANG Yu, WEI Wenqiang, WANG Mingrong, HAO Jiajie. P4HA2 promotes proliferation of esophageal squamous carcinoma cells via activating the EGFR/AKT/S6 signaling pathway[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(2): 87-94,101.

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P4HA2通过激活EGFR/AKT/S6信号通路促进食管鳞癌细胞的增殖

P4HA2 promotes proliferation of esophageal squamous carcinoma cells via activating the EGFR/AKT/S6 signaling pathway

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