LRG1 Is Involved in the Progression of Ovarian Cancer via Modulating FAK/AKT Signaling Pathway

Background: Rapid progression and early metastasis remain the main cause of high mortality in epithelial ovarian cancer (EOC) patients. The objective of this study was to explore the mechanisms of EOC progression and detect the function of leucine-rich alpha-2-glycoprotein 1 (LRG1) in modulating the...

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Main Authors: Dongling Wu, Weiwei Xie, Xin Chen, Huizhen Sun
Format: Article
Language:English
Published: IMR Press 2023-05-01
Series:Frontiers in Bioscience-Landmark
Subjects:
Online Access:https://www.imrpress.com/journal/FBL/28/5/10.31083/j.fbl2805101
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author Dongling Wu
Weiwei Xie
Xin Chen
Huizhen Sun
author_facet Dongling Wu
Weiwei Xie
Xin Chen
Huizhen Sun
author_sort Dongling Wu
collection DOAJ
description Background: Rapid progression and early metastasis remain the main cause of high mortality in epithelial ovarian cancer (EOC) patients. The objective of this study was to explore the mechanisms of EOC progression and detect the function of leucine-rich alpha-2-glycoprotein 1 (LRG1) in modulating the pathologic process. Methods: Ultracentrifugation was initially performed to extract exosomes from the urine samples of EOC patients and healthy female subjects. Mass spectrometry (MS) was employed to analyze differentially expressed proteins. Survival analysis was performed to examine the association between LRG1 levels and the prognosis of EOC patients. LRG1 silencing ovarian cancer cell lines were built and cell migration was further evaluated via wound healing and transwell assays. Immunoblot, immunofluorescence and immunohistochemistry analyses were performed. A subcutaneous tumor model was established to study the function of LRG1 in vivo. Results: Exosomal LRG1 was specifically expressed in urine samples of EOC patients and high LRG1 levels were significantly associated with poor prognosis. Function analyses showed that LRG1 was associated with ovarian cancer migration and progression. Mechanistically, LRG1 was significantly related to the focal adhesion kinase/protein kinase B (FAK/AKT) signaling pathway. Conclusions: LRG1 participated in progression and metastasis of ovarian cancer via activation of the FAK/AKT pathway probably.
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spelling doaj.art-59d1497265bc4c6980950cf38e559c562023-06-01T02:53:04ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-05-0128510110.31083/j.fbl2805101S2768-6701(23)00759-1LRG1 Is Involved in the Progression of Ovarian Cancer via Modulating FAK/AKT Signaling PathwayDongling Wu0Weiwei Xie1Xin Chen2Huizhen Sun3Department of Obstetrics and Gynecology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200092 Shanghai, ChinaDepartment of Obstetrics and Gynecology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200092 Shanghai, ChinaDepartment of Obstetrics and Gynecology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200092 Shanghai, ChinaDepartment of Obstetrics and Gynecology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200092 Shanghai, ChinaBackground: Rapid progression and early metastasis remain the main cause of high mortality in epithelial ovarian cancer (EOC) patients. The objective of this study was to explore the mechanisms of EOC progression and detect the function of leucine-rich alpha-2-glycoprotein 1 (LRG1) in modulating the pathologic process. Methods: Ultracentrifugation was initially performed to extract exosomes from the urine samples of EOC patients and healthy female subjects. Mass spectrometry (MS) was employed to analyze differentially expressed proteins. Survival analysis was performed to examine the association between LRG1 levels and the prognosis of EOC patients. LRG1 silencing ovarian cancer cell lines were built and cell migration was further evaluated via wound healing and transwell assays. Immunoblot, immunofluorescence and immunohistochemistry analyses were performed. A subcutaneous tumor model was established to study the function of LRG1 in vivo. Results: Exosomal LRG1 was specifically expressed in urine samples of EOC patients and high LRG1 levels were significantly associated with poor prognosis. Function analyses showed that LRG1 was associated with ovarian cancer migration and progression. Mechanistically, LRG1 was significantly related to the focal adhesion kinase/protein kinase B (FAK/AKT) signaling pathway. Conclusions: LRG1 participated in progression and metastasis of ovarian cancer via activation of the FAK/AKT pathway probably.https://www.imrpress.com/journal/FBL/28/5/10.31083/j.fbl2805101lrg1progressionfakaktexosomeovarian cancer
spellingShingle Dongling Wu
Weiwei Xie
Xin Chen
Huizhen Sun
LRG1 Is Involved in the Progression of Ovarian Cancer via Modulating FAK/AKT Signaling Pathway
Frontiers in Bioscience-Landmark
lrg1
progression
fak
akt
exosome
ovarian cancer
title LRG1 Is Involved in the Progression of Ovarian Cancer via Modulating FAK/AKT Signaling Pathway
title_full LRG1 Is Involved in the Progression of Ovarian Cancer via Modulating FAK/AKT Signaling Pathway
title_fullStr LRG1 Is Involved in the Progression of Ovarian Cancer via Modulating FAK/AKT Signaling Pathway
title_full_unstemmed LRG1 Is Involved in the Progression of Ovarian Cancer via Modulating FAK/AKT Signaling Pathway
title_short LRG1 Is Involved in the Progression of Ovarian Cancer via Modulating FAK/AKT Signaling Pathway
title_sort lrg1 is involved in the progression of ovarian cancer via modulating fak akt signaling pathway
topic lrg1
progression
fak
akt
exosome
ovarian cancer
url https://www.imrpress.com/journal/FBL/28/5/10.31083/j.fbl2805101
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