KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway

Yi Song,1,* Huiping Yuan,2,* Jia Wang,3 Yuhe Wu,4 Yuhong Xiao,5 Shengxun Mao1 1Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China; 2Department of Gastrointestinal Surgery, Cangzhou Hospital of Integrate...

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Main Authors: Song Y, Yuan H, Wang J, Wu Y, Xiao Y, Mao S
Format: Article
Language:English
Published: Dove Medical Press 2020-05-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/klhl22-regulates-the-emt-and-proliferation-in-colorectal-cancer-cells--peer-reviewed-article-CMAR
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author Song Y
Yuan H
Wang J
Wu Y
Xiao Y
Mao S
author_facet Song Y
Yuan H
Wang J
Wu Y
Xiao Y
Mao S
author_sort Song Y
collection DOAJ
description Yi Song,1,* Huiping Yuan,2,* Jia Wang,3 Yuhe Wu,4 Yuhong Xiao,5 Shengxun Mao1 1Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China; 2Department of Gastrointestinal Surgery, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou, Hebei 061000, People’s Republic of China; 3Radiotherapy and Chemotherapy Department, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou, Hebei 061000, People’s Republic of China; 4Basic Medical College, Gannan Medical University, Ganzhou, JiangXi 341000, People’s Republic of China; 5Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengxun Mao Email maoshengxun@126.comBackground: Colorectal cancer (CRC) is one of the most common aggressive malignancies. KLHL22 functions as a tumor suppressor, and previous findings have demonstrated that KLHL22 can regulate the development of breast cancer and CRC. However, few studies have investigated the role of KLHL22 in CRC cell epithelial-to-mesenchymal transition (EMT) and proliferation. The current study aimed to detect the role of KLHL22 in CRC cell proliferation and EMT and to elucidate the probable molecular mechanisms through which KLHL22 is involved with these processes.Materials and Methods: Transwell invasion, MTT, immunohistochemistry and Western blotting assays were performed to evaluate the migration, invasion and proliferation abilities of CRC cells, and the levels of active molecules involved in the Wnt/β-catenin signaling pathway were examined through Western blotting analysis. In addition, the in vivo function of KLHL22 was assessed using a tumor xenograft model.Results: KLHL22 expression was weaker in CRC tissues than in nonmalignant tissues and could inhibit cell invasion, migration, and proliferation in vitro. Furthermore, the regulatory effects of KLHL22 on EMT were partially attributed to the Wnt/β-catenin signaling pathway. The in vivo results also showed that KLHL22 modulated CRC tumorigenesis.Conclusion: KLHL22 can regulate the activity of GSK-3β to influence the level of PI3K, and this regulation promotes EMT inhibition partially through the Wnt/β-catenin signaling pathway.Keywords: colorectal cancer, KLHL22, Wnt, EMT
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spelling doaj.art-3bfffcb3ea504580a958786feeb11fe82022-12-21T19:18:47ZengDove Medical PressCancer Management and Research1179-13222020-05-01Volume 123981399354139KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling PathwaySong YYuan HWang JWu YXiao YMao SYi Song,1,* Huiping Yuan,2,* Jia Wang,3 Yuhe Wu,4 Yuhong Xiao,5 Shengxun Mao1 1Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China; 2Department of Gastrointestinal Surgery, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou, Hebei 061000, People’s Republic of China; 3Radiotherapy and Chemotherapy Department, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou, Hebei 061000, People’s Republic of China; 4Basic Medical College, Gannan Medical University, Ganzhou, JiangXi 341000, People’s Republic of China; 5Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengxun Mao Email maoshengxun@126.comBackground: Colorectal cancer (CRC) is one of the most common aggressive malignancies. KLHL22 functions as a tumor suppressor, and previous findings have demonstrated that KLHL22 can regulate the development of breast cancer and CRC. However, few studies have investigated the role of KLHL22 in CRC cell epithelial-to-mesenchymal transition (EMT) and proliferation. The current study aimed to detect the role of KLHL22 in CRC cell proliferation and EMT and to elucidate the probable molecular mechanisms through which KLHL22 is involved with these processes.Materials and Methods: Transwell invasion, MTT, immunohistochemistry and Western blotting assays were performed to evaluate the migration, invasion and proliferation abilities of CRC cells, and the levels of active molecules involved in the Wnt/β-catenin signaling pathway were examined through Western blotting analysis. In addition, the in vivo function of KLHL22 was assessed using a tumor xenograft model.Results: KLHL22 expression was weaker in CRC tissues than in nonmalignant tissues and could inhibit cell invasion, migration, and proliferation in vitro. Furthermore, the regulatory effects of KLHL22 on EMT were partially attributed to the Wnt/β-catenin signaling pathway. The in vivo results also showed that KLHL22 modulated CRC tumorigenesis.Conclusion: KLHL22 can regulate the activity of GSK-3β to influence the level of PI3K, and this regulation promotes EMT inhibition partially through the Wnt/β-catenin signaling pathway.Keywords: colorectal cancer, KLHL22, Wnt, EMThttps://www.dovepress.com/klhl22-regulates-the-emt-and-proliferation-in-colorectal-cancer-cells--peer-reviewed-article-CMARcolorectal cancerklhl22wntemt
spellingShingle Song Y
Yuan H
Wang J
Wu Y
Xiao Y
Mao S
KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway
Cancer Management and Research
colorectal cancer
klhl22
wnt
emt
title KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway
title_full KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway
title_fullStr KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway
title_full_unstemmed KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway
title_short KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway
title_sort klhl22 regulates the emt and proliferation in colorectal cancer cells in part via the wnt beta catenin signaling pathway
topic colorectal cancer
klhl22
wnt
emt
url https://www.dovepress.com/klhl22-regulates-the-emt-and-proliferation-in-colorectal-cancer-cells--peer-reviewed-article-CMAR
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