PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway
Background: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a co-activator of estrogen receptors alpha, was confirmed to be directly associated with the oncogenic process of multiple cancers, especially hormone-dependent cancers. The purpose of our research was to explore the biologica...
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doaj-47d394fe678c439788e2e438f2707ac22020-11-25T00:34:37ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-02-01910.3389/fonc.2019.01423461305PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK PathwayHongzhu Yan0Hongzhu Yan1Yanling Sun2Qian Wu3Zhe Wu4Meichun Hu5Yuanpeng Sun6Yusi Liu7Zi Ma8Shangqin Liu9Wuhan Xiao10Fuxing Liu11Zhifeng Ning12Basic Medical School, Hubei University of Science and Technology, Xianning, ChinaInstitute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, ChinaBasic Medical School, Hubei University of Science and Technology, Xianning, ChinaBasic Medical School, Hubei University of Science and Technology, Xianning, ChinaBasic Medical School, Hubei University of Science and Technology, Xianning, ChinaBasic Medical School, Hubei University of Science and Technology, Xianning, ChinaBasic Medical School, Hubei University of Science and Technology, Xianning, ChinaBasic Medical School, Hubei University of Science and Technology, Xianning, ChinaWuhan University Zhongnan Hospital, Wuhan, ChinaWuhan University Zhongnan Hospital, Wuhan, ChinaThe Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaBasic Medical School, Hubei University of Science and Technology, Xianning, ChinaBasic Medical School, Hubei University of Science and Technology, Xianning, ChinaBackground: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a co-activator of estrogen receptors alpha, was confirmed to be directly associated with the oncogenic process of multiple cancers, especially hormone-dependent cancers. The purpose of our research was to explore the biological function, clinical significance, and therapeutic targeted value of PELP1 in gastric cancer (GC).Methods: The expression status of PELP1 in GC cell lines or tissues was analyzed through bioinformatics data mining. Thirty-six GC tissue chip was applied to demonstrate the results of bioinformatics data mining assayed by immunohistochemical method. The expression status of PELP1 in GC cell lines was also analyzed using western blot. Correlation analysis between PELP1 expression and clinicopathological parameter was performed. Kaplan-Meier survival analysis was applied to analyze the relationship between PELP1 expression and total survival time. Three pairs of siRNA were designed to silence the expression of PELP1 in GC. After PELP1 was silenced by siRNA or activated by saRNA, the growth, plate colony formation, migration and invasion ability of the GC cell or normal gastric epithelium cell line was tested in vitro. Cell cycle was tested by flow cytometry. Nude mice xenograft experiment was performed after PELP1 was silenced. The downstream molecular pathway regulated by PELP1 was explored. Molecular docking tool was applied to combine chlorpromazine with PELP1. The inhibitory effect of chlorpromazine in GC was assayed, then it was tested whether PELP1 was a therapeutic target of chlorpromazine in GC.Results: PELP1 expression was elevated in GC cell lines and clinical GC tissue samples. PELP1 silence by siRNA compromised the malignant traits of GC. PELP1 expression positively correlated with tumor invasion depth, lymph node metastasis, tissue grade, TNM stage, but had no correlation with patient age, sex, tumor size, and tumor numbers. Kaplan-Meier survival analysis revealed high PELP1 expression had a shorter survival period in GC patients after follow-up. Q-PCR and western blot revealed PELP1 suppression in GC decreased expression of the c-Src-PI3K-ERK pathway. It was also implied that chlorpromazine (CPZ) can inhibit the malignant traits of GC and downregulate the expression of PELP1.Conclusions: In a word, PELP1 is an oncogene in gastric cancer and c-Src-PI3K-ERK pathway activation may be responsible for its tumorigenesis, PELP1 may be a potential therapeutic target of chlorpromazine in GC.https://www.frontiersin.org/article/10.3389/fonc.2019.01423/fullPELP1oncogenemaster genegastric cancerc-Src-PI3K-ERK pathwaychlorpromazine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hongzhu Yan Hongzhu Yan Yanling Sun Qian Wu Zhe Wu Meichun Hu Yuanpeng Sun Yusi Liu Zi Ma Shangqin Liu Wuhan Xiao Fuxing Liu Zhifeng Ning |
spellingShingle |
Hongzhu Yan Hongzhu Yan Yanling Sun Qian Wu Zhe Wu Meichun Hu Yuanpeng Sun Yusi Liu Zi Ma Shangqin Liu Wuhan Xiao Fuxing Liu Zhifeng Ning PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway Frontiers in Oncology PELP1 oncogene master gene gastric cancer c-Src-PI3K-ERK pathway chlorpromazine |
author_facet |
Hongzhu Yan Hongzhu Yan Yanling Sun Qian Wu Zhe Wu Meichun Hu Yuanpeng Sun Yusi Liu Zi Ma Shangqin Liu Wuhan Xiao Fuxing Liu Zhifeng Ning |
author_sort |
Hongzhu Yan |
title |
PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway |
title_short |
PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway |
title_full |
PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway |
title_fullStr |
PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway |
title_full_unstemmed |
PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway |
title_sort |
pelp1 suppression inhibits gastric cancer through downregulation of c-src-pi3k-erk pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2020-02-01 |
description |
Background: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a co-activator of estrogen receptors alpha, was confirmed to be directly associated with the oncogenic process of multiple cancers, especially hormone-dependent cancers. The purpose of our research was to explore the biological function, clinical significance, and therapeutic targeted value of PELP1 in gastric cancer (GC).Methods: The expression status of PELP1 in GC cell lines or tissues was analyzed through bioinformatics data mining. Thirty-six GC tissue chip was applied to demonstrate the results of bioinformatics data mining assayed by immunohistochemical method. The expression status of PELP1 in GC cell lines was also analyzed using western blot. Correlation analysis between PELP1 expression and clinicopathological parameter was performed. Kaplan-Meier survival analysis was applied to analyze the relationship between PELP1 expression and total survival time. Three pairs of siRNA were designed to silence the expression of PELP1 in GC. After PELP1 was silenced by siRNA or activated by saRNA, the growth, plate colony formation, migration and invasion ability of the GC cell or normal gastric epithelium cell line was tested in vitro. Cell cycle was tested by flow cytometry. Nude mice xenograft experiment was performed after PELP1 was silenced. The downstream molecular pathway regulated by PELP1 was explored. Molecular docking tool was applied to combine chlorpromazine with PELP1. The inhibitory effect of chlorpromazine in GC was assayed, then it was tested whether PELP1 was a therapeutic target of chlorpromazine in GC.Results: PELP1 expression was elevated in GC cell lines and clinical GC tissue samples. PELP1 silence by siRNA compromised the malignant traits of GC. PELP1 expression positively correlated with tumor invasion depth, lymph node metastasis, tissue grade, TNM stage, but had no correlation with patient age, sex, tumor size, and tumor numbers. Kaplan-Meier survival analysis revealed high PELP1 expression had a shorter survival period in GC patients after follow-up. Q-PCR and western blot revealed PELP1 suppression in GC decreased expression of the c-Src-PI3K-ERK pathway. It was also implied that chlorpromazine (CPZ) can inhibit the malignant traits of GC and downregulate the expression of PELP1.Conclusions: In a word, PELP1 is an oncogene in gastric cancer and c-Src-PI3K-ERK pathway activation may be responsible for its tumorigenesis, PELP1 may be a potential therapeutic target of chlorpromazine in GC. |
topic |
PELP1 oncogene master gene gastric cancer c-Src-PI3K-ERK pathway chlorpromazine |
url |
https://www.frontiersin.org/article/10.3389/fonc.2019.01423/full |
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