Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 Pathway
Metastasis is associated with poor prognosis in cancer and is a multistep process that includes invasion and migration. Several epigenetic factors are involved in this process, including chromobox protein homolog 8 (CBX8). Here, we show that CBX8 is overexpressed in many cancers compared with normal...
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2020-12-01
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doaj-68dde3b35e96420ab46784f422f7b7c72020-12-19T05:09:11ZengElsevierMolecular Therapy: Oncolytics2372-77052020-12-0119188196Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 PathwayYongsheng Jia0Yujun Wang1Cuicui Zhang2Mike Yue Chen3Thyroid and Neck Department, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Division of Neurosurgery, City of Hope and Beckman Research Institute, Duarte, CA, USADivision of Neurosurgery, City of Hope and Beckman Research Institute, Duarte, CA, USADepartment of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaDivision of Neurosurgery, City of Hope and Beckman Research Institute, Duarte, CA, USA; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Corresponding author: Mike Yue Chen, Division of Neurosurgery, City of Hope and Beckman Research Institute, City of Hope, Duarte, CA 91010.Metastasis is associated with poor prognosis in cancer and is a multistep process that includes invasion and migration. Several epigenetic factors are involved in this process, including chromobox protein homolog 8 (CBX8). Here, we show that CBX8 is overexpressed in many cancers compared with normal tissues. Functional analyses indicated that CBX8 promoted invasion and migration in glioblastoma, breast cancer, and lung cancer in vitro and in vivo. WNK2 was identified as a target gene of CBX8, which interacted with the WNK2 promoter to suppress WNK2 expression and activity. WNK2 acted as an antioncogene, and decreased WNK2 levels resulted in high activity of matrix metalloprotease (MMP)-2 and RAC1, which play a central role in invasion and migration, respectively. There was a positive relationship between MMP2 and RAC1 activity in CBX8-modulated cell lines. In addition, WNK2 negatively regulated MMP2 and RAC1 activity. Collectively, the results indicated that CBX8 promoted invasion and migration by targeting WNK2, which resulted in increased RAC1 and MMP2 expression and activity. Therefore, CBX8 may be a novel therapeutic target to treat metastatic cancers.http://www.sciencedirect.com/science/article/pii/S2372770520301510CBX8WNK2MMP2RAC1metastasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yongsheng Jia Yujun Wang Cuicui Zhang Mike Yue Chen |
spellingShingle |
Yongsheng Jia Yujun Wang Cuicui Zhang Mike Yue Chen Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 Pathway Molecular Therapy: Oncolytics CBX8 WNK2 MMP2 RAC1 metastasis |
author_facet |
Yongsheng Jia Yujun Wang Cuicui Zhang Mike Yue Chen |
author_sort |
Yongsheng Jia |
title |
Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 Pathway |
title_short |
Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 Pathway |
title_full |
Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 Pathway |
title_fullStr |
Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 Pathway |
title_full_unstemmed |
Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 Pathway |
title_sort |
upregulated cbx8 promotes cancer metastasis via the wnk2/mmp2 pathway |
publisher |
Elsevier |
series |
Molecular Therapy: Oncolytics |
issn |
2372-7705 |
publishDate |
2020-12-01 |
description |
Metastasis is associated with poor prognosis in cancer and is a multistep process that includes invasion and migration. Several epigenetic factors are involved in this process, including chromobox protein homolog 8 (CBX8). Here, we show that CBX8 is overexpressed in many cancers compared with normal tissues. Functional analyses indicated that CBX8 promoted invasion and migration in glioblastoma, breast cancer, and lung cancer in vitro and in vivo. WNK2 was identified as a target gene of CBX8, which interacted with the WNK2 promoter to suppress WNK2 expression and activity. WNK2 acted as an antioncogene, and decreased WNK2 levels resulted in high activity of matrix metalloprotease (MMP)-2 and RAC1, which play a central role in invasion and migration, respectively. There was a positive relationship between MMP2 and RAC1 activity in CBX8-modulated cell lines. In addition, WNK2 negatively regulated MMP2 and RAC1 activity. Collectively, the results indicated that CBX8 promoted invasion and migration by targeting WNK2, which resulted in increased RAC1 and MMP2 expression and activity. Therefore, CBX8 may be a novel therapeutic target to treat metastatic cancers. |
topic |
CBX8 WNK2 MMP2 RAC1 metastasis |
url |
http://www.sciencedirect.com/science/article/pii/S2372770520301510 |
work_keys_str_mv |
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