Adipocyte-derived CCDC3 promotes tumorigenesis in epithelial ovarian cancer through the Wnt/ß-catenin signalling pathway

Introduction: Epithelial ovarian cancer (EOC) is a highly aggressive disease whose unique metastatic site is the omentum. Coiled-coil domain containing 3 (CCDC3) is an adipocyte-derived secreted protein that is specifically elevated in omental adipose tissue. However, its function is still unknown....

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Main Authors: Fen Wang, Feng Jin, Shanshan Peng, Chen Li, Li Wang, Shubin Wang
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Biochemistry and Biophysics Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580823000882
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author Fen Wang
Feng Jin
Shanshan Peng
Chen Li
Li Wang
Shubin Wang
author_facet Fen Wang
Feng Jin
Shanshan Peng
Chen Li
Li Wang
Shubin Wang
author_sort Fen Wang
collection DOAJ
description Introduction: Epithelial ovarian cancer (EOC) is a highly aggressive disease whose unique metastatic site is the omentum. Coiled-coil domain containing 3 (CCDC3) is an adipocyte-derived secreted protein that is specifically elevated in omental adipose tissue. However, its function is still unknown. Material and methods: Initially, a Kaplan–Meier plot was applied to evaluate the prognostic value of CCDC3 expression in patients with EOC. A bioinformatics analysis was next used to explore the biological function of CCDC3 in EOC. Western blot, quantitative real-time polymerase chain reaction, and in vitro invasion and migration assays were performed using SKOV3 cells and CCDC3 secreted by rat adipocytes to analyzes the impact of CCDC3 on EOC and the underlying mechanism. Results: Overexpression of CCDC3 was associated with poor prognosis of EOC. CCDC3 interacted with multiple key signalling pathways, including the Wnt/β-catenin pathway. EOC cellular proliferation, migration, and invasion were promoted in vitro when co-cultured with CCDC3 enriched conditioned medium, and this tumour-promoting effect was induced by activating the Wnt/β-catenin pathway. Furthermore, the epithelial-mesenchymal transition of EOC cells was reversed after CCDC3 silencing. Conclusions: Our results support that CCDC3 promotes EOC tumorigenesis through the Wnt/β-catenin pathway and that CCDC3 may serve as a novel prognostic biomarker and therapeutic target for metastatic EOC.
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spelling doaj.art-1c8e8d617b64400d9e2ee54d904320262023-10-13T13:54:54ZengElsevierBiochemistry and Biophysics Reports2405-58082023-09-0135101507Adipocyte-derived CCDC3 promotes tumorigenesis in epithelial ovarian cancer through the Wnt/ß-catenin signalling pathwayFen Wang0Feng Jin1Shanshan Peng2Chen Li3Li Wang4Shubin Wang5Department of Medical Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute of Shenzhen-PKU-HKUST Medical Center, Shenzhen 518036, China; Corresponding author. Department of Medical Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute of Shenzhen-PKU-HKUST Medical Center, Shenzhen 518036, China.Department of Medical Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute of Shenzhen-PKU-HKUST Medical Center, Shenzhen 518036, ChinaDepartment of Gynecology, Shenzhen Baoan Maternal and Child Healthcare Hospital, Shenzhen 518000, ChinaDepartment of Medical Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute of Shenzhen-PKU-HKUST Medical Center, Shenzhen 518036, ChinaDepartment of Medical Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute of Shenzhen-PKU-HKUST Medical Center, Shenzhen 518036, ChinaDepartment of Medical Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute of Shenzhen-PKU-HKUST Medical Center, Shenzhen 518036, ChinaIntroduction: Epithelial ovarian cancer (EOC) is a highly aggressive disease whose unique metastatic site is the omentum. Coiled-coil domain containing 3 (CCDC3) is an adipocyte-derived secreted protein that is specifically elevated in omental adipose tissue. However, its function is still unknown. Material and methods: Initially, a Kaplan–Meier plot was applied to evaluate the prognostic value of CCDC3 expression in patients with EOC. A bioinformatics analysis was next used to explore the biological function of CCDC3 in EOC. Western blot, quantitative real-time polymerase chain reaction, and in vitro invasion and migration assays were performed using SKOV3 cells and CCDC3 secreted by rat adipocytes to analyzes the impact of CCDC3 on EOC and the underlying mechanism. Results: Overexpression of CCDC3 was associated with poor prognosis of EOC. CCDC3 interacted with multiple key signalling pathways, including the Wnt/β-catenin pathway. EOC cellular proliferation, migration, and invasion were promoted in vitro when co-cultured with CCDC3 enriched conditioned medium, and this tumour-promoting effect was induced by activating the Wnt/β-catenin pathway. Furthermore, the epithelial-mesenchymal transition of EOC cells was reversed after CCDC3 silencing. Conclusions: Our results support that CCDC3 promotes EOC tumorigenesis through the Wnt/β-catenin pathway and that CCDC3 may serve as a novel prognostic biomarker and therapeutic target for metastatic EOC.http://www.sciencedirect.com/science/article/pii/S2405580823000882CCDC3Wnt/β-cateninEpithelial ovarian cancerEpithelial-mesenchymal transitionOmental metastasis
spellingShingle Fen Wang
Feng Jin
Shanshan Peng
Chen Li
Li Wang
Shubin Wang
Adipocyte-derived CCDC3 promotes tumorigenesis in epithelial ovarian cancer through the Wnt/ß-catenin signalling pathway
Biochemistry and Biophysics Reports
CCDC3
Wnt/β-catenin
Epithelial ovarian cancer
Epithelial-mesenchymal transition
Omental metastasis
title Adipocyte-derived CCDC3 promotes tumorigenesis in epithelial ovarian cancer through the Wnt/ß-catenin signalling pathway
title_full Adipocyte-derived CCDC3 promotes tumorigenesis in epithelial ovarian cancer through the Wnt/ß-catenin signalling pathway
title_fullStr Adipocyte-derived CCDC3 promotes tumorigenesis in epithelial ovarian cancer through the Wnt/ß-catenin signalling pathway
title_full_unstemmed Adipocyte-derived CCDC3 promotes tumorigenesis in epithelial ovarian cancer through the Wnt/ß-catenin signalling pathway
title_short Adipocyte-derived CCDC3 promotes tumorigenesis in epithelial ovarian cancer through the Wnt/ß-catenin signalling pathway
title_sort adipocyte derived ccdc3 promotes tumorigenesis in epithelial ovarian cancer through the wnt ss catenin signalling pathway
topic CCDC3
Wnt/β-catenin
Epithelial ovarian cancer
Epithelial-mesenchymal transition
Omental metastasis
url http://www.sciencedirect.com/science/article/pii/S2405580823000882
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