Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/β-Catenin Signaling Pathway
The abnormal elevation of sulfiredoxin (Srx/SRXN1)—an antioxidant enzyme whose main function is to protect against oxidative stress—has been shown to be closely correlated with the progression of several types of cancer, including human cervical cancer. However, the molecular mechanism by which Srx...
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doaj-ae96adfff53048aab963dc951fcf651c2020-11-24T23:06:48ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-04-0118591710.3390/ijms18050917ijms18050917Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/β-Catenin Signaling PathwayKangyun Lan0Yuni Zhao1Yue Fan2Binbin Ma3Shanshan Yang4Qin Liu5Hua Linghu6Hui Wang7Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaThe abnormal elevation of sulfiredoxin (Srx/SRXN1)—an antioxidant enzyme whose main function is to protect against oxidative stress—has been shown to be closely correlated with the progression of several types of cancer, including human cervical cancer. However, the molecular mechanism by which Srx promotes tumor progression, especially cancer metastasis in cervical cancer, has not been elucidated. Here, we show that Srx expression gradually increases during the progression of human cervical cancer and its expression level is closely correlated with lymph node metastasis. Our study also reveals a significant positive correlation between the expression of Srx and β-catenin in cervical cancer tissues. Loss-of-function studies demonstrate that Srx knockdown using a lentiviral vector-mediated specific shRNA decreases the migration and invasion capacity in HeLa (human papilloma virus 18 type cervical cancer cell line) and SiHa SiHa (cervical squamous cancer cell line). Notably, the exact opposite effects were observed in gain-of-function experiments in C-33A cells. Mechanistically, downregulation or upregulation of Srx leads to an altered expression of proteins associated with the Wnt/β-catenin signaling pathway. Furthermore, blockage of the Wnt/β-catenin signaling pathway contributed to attenuated Srx expression and resulted in significant inhibition of cell migration and invasion in cervical cancer cell lines. Combined, Srx might be an oncoprotein in cervical cancer, playing critical roles in activating the Wnt/β-catenin signaling pathway; it may therefore be a therapeutic target for cervical cancer.http://www.mdpi.com/1422-0067/18/5/917sulfiredoxincervical cancermetastasisWnt/β-catenin signaling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kangyun Lan Yuni Zhao Yue Fan Binbin Ma Shanshan Yang Qin Liu Hua Linghu Hui Wang |
spellingShingle |
Kangyun Lan Yuni Zhao Yue Fan Binbin Ma Shanshan Yang Qin Liu Hua Linghu Hui Wang Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/β-Catenin Signaling Pathway International Journal of Molecular Sciences sulfiredoxin cervical cancer metastasis Wnt/β-catenin signaling |
author_facet |
Kangyun Lan Yuni Zhao Yue Fan Binbin Ma Shanshan Yang Qin Liu Hua Linghu Hui Wang |
author_sort |
Kangyun Lan |
title |
Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/β-Catenin Signaling Pathway |
title_short |
Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/β-Catenin Signaling Pathway |
title_full |
Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/β-Catenin Signaling Pathway |
title_fullStr |
Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/β-Catenin Signaling Pathway |
title_full_unstemmed |
Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/β-Catenin Signaling Pathway |
title_sort |
sulfiredoxin may promote cervical cancer metastasis via wnt/β-catenin signaling pathway |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-04-01 |
description |
The abnormal elevation of sulfiredoxin (Srx/SRXN1)—an antioxidant enzyme whose main function is to protect against oxidative stress—has been shown to be closely correlated with the progression of several types of cancer, including human cervical cancer. However, the molecular mechanism by which Srx promotes tumor progression, especially cancer metastasis in cervical cancer, has not been elucidated. Here, we show that Srx expression gradually increases during the progression of human cervical cancer and its expression level is closely correlated with lymph node metastasis. Our study also reveals a significant positive correlation between the expression of Srx and β-catenin in cervical cancer tissues. Loss-of-function studies demonstrate that Srx knockdown using a lentiviral vector-mediated specific shRNA decreases the migration and invasion capacity in HeLa (human papilloma virus 18 type cervical cancer cell line) and SiHa SiHa (cervical squamous cancer cell line). Notably, the exact opposite effects were observed in gain-of-function experiments in C-33A cells. Mechanistically, downregulation or upregulation of Srx leads to an altered expression of proteins associated with the Wnt/β-catenin signaling pathway. Furthermore, blockage of the Wnt/β-catenin signaling pathway contributed to attenuated Srx expression and resulted in significant inhibition of cell migration and invasion in cervical cancer cell lines. Combined, Srx might be an oncoprotein in cervical cancer, playing critical roles in activating the Wnt/β-catenin signaling pathway; it may therefore be a therapeutic target for cervical cancer. |
topic |
sulfiredoxin cervical cancer metastasis Wnt/β-catenin signaling |
url |
http://www.mdpi.com/1422-0067/18/5/917 |
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