Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma
Elevated SOX2 protein levels are closely correlated with the increased incidence of esophageal squamous cell carcinoma (ESCC). However, establishing effective target measures for ESCC treatments continue to be researched. It has been previously proposed that SOX2 represents a potential therapeutic t...
Main Authors: | , , , , , , , , , , , , , , , , |
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Language: | English |
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Elsevier
2022-09-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222006989 |
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author | Zhuo Wang Junkai Wang Hongzhou Zhao Tingting Zhao Yunyun Chen Ming Jiang Shihui Zhang Yuxuan Wei Jiaying Zhang Yijian Zhou Songlin Shi Zhichao Fu Yaxin Yang Yujun Zhang Ling Yang Jianwen Que Kuancan Liu |
author_facet | Zhuo Wang Junkai Wang Hongzhou Zhao Tingting Zhao Yunyun Chen Ming Jiang Shihui Zhang Yuxuan Wei Jiaying Zhang Yijian Zhou Songlin Shi Zhichao Fu Yaxin Yang Yujun Zhang Ling Yang Jianwen Que Kuancan Liu |
author_sort | Zhuo Wang |
collection | DOAJ |
description | Elevated SOX2 protein levels are closely correlated with the increased incidence of esophageal squamous cell carcinoma (ESCC). However, establishing effective target measures for ESCC treatments continue to be researched. It has been previously proposed that SOX2 represents a potential therapeutic target for ESCC. Here, we found that the enzyme Poly(ADP-Ribose) polymerase 1 (PARP1) enriched in ESCCs interact with SOX2. Inhibition of PARP1 with 3-aminobenzamide (3-ABA) or shRNA knockdown reduced the proliferation of ESCCs, accompanied by decreased protein levels of SOX2. RNA sequencing demonstrated that PARP1 inhibition affected multiple signaling pathways involved in cancer cell proliferation. Additionally, 3-ABA synergistically suppressed the growth of ESCC cells when combined with cisplatin, and metformin potentiated the suppressive effect of 3-ABA on ESCC cell growth. Together these findings suggest that targeting SOX2 binding partner PARP1 provides a possible avenue to treat patients with high levels of SOX2. |
first_indexed | 2024-04-11T14:14:24Z |
format | Article |
id | doaj.art-35c29b9a71884adf930a993d8ca5cf56 |
institution | Directory Open Access Journal |
issn | 0753-3322 |
language | English |
last_indexed | 2024-04-11T14:14:24Z |
publishDate | 2022-09-01 |
publisher | Elsevier |
record_format | Article |
series | Biomedicine & Pharmacotherapy |
spelling | doaj.art-35c29b9a71884adf930a993d8ca5cf562022-12-22T04:19:36ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-09-01153113309Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinomaZhuo Wang0Junkai Wang1Hongzhou Zhao2Tingting Zhao3Yunyun Chen4Ming Jiang5Shihui Zhang6Yuxuan Wei7Jiaying Zhang8Yijian Zhou9Songlin Shi10Zhichao Fu11Yaxin Yang12Yujun Zhang13Ling Yang14Jianwen Que15Kuancan Liu16Central Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaCentral Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaCentral Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaCentral Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaCentral Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaDepartment of Gastroenterology of The Children's Hospital, Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, ChinaCentre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4UU, UKCentral Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Life Science, Xiamen University, Xiamen, Fujian 361102, ChinaCentral Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaDepartment of radiotherapy, 900 Hospital of the Joint Logistics Team (Dongfang Hospital, Xiamen University), Fuzhou, Fujian 350025, ChinaDepartment of Biology, University of Rochester, NY 14627, USASchool of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Medicine, Xiamen University, Xiamen, Fujian 361102, ChinaDepartment of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Correspondence to: Department of Medicine, Columbia University, Medical Centre, USA.Central Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; Correspondence to: School of Medicine, Xiamen University, China.Elevated SOX2 protein levels are closely correlated with the increased incidence of esophageal squamous cell carcinoma (ESCC). However, establishing effective target measures for ESCC treatments continue to be researched. It has been previously proposed that SOX2 represents a potential therapeutic target for ESCC. Here, we found that the enzyme Poly(ADP-Ribose) polymerase 1 (PARP1) enriched in ESCCs interact with SOX2. Inhibition of PARP1 with 3-aminobenzamide (3-ABA) or shRNA knockdown reduced the proliferation of ESCCs, accompanied by decreased protein levels of SOX2. RNA sequencing demonstrated that PARP1 inhibition affected multiple signaling pathways involved in cancer cell proliferation. Additionally, 3-ABA synergistically suppressed the growth of ESCC cells when combined with cisplatin, and metformin potentiated the suppressive effect of 3-ABA on ESCC cell growth. Together these findings suggest that targeting SOX2 binding partner PARP1 provides a possible avenue to treat patients with high levels of SOX2.http://www.sciencedirect.com/science/article/pii/S0753332222006989Esophageal squamous cell carcinomaSOX2PARP13-ABAMetformin |
spellingShingle | Zhuo Wang Junkai Wang Hongzhou Zhao Tingting Zhao Yunyun Chen Ming Jiang Shihui Zhang Yuxuan Wei Jiaying Zhang Yijian Zhou Songlin Shi Zhichao Fu Yaxin Yang Yujun Zhang Ling Yang Jianwen Que Kuancan Liu Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma Biomedicine & Pharmacotherapy Esophageal squamous cell carcinoma SOX2 PARP1 3-ABA Metformin |
title | Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma |
title_full | Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma |
title_fullStr | Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma |
title_full_unstemmed | Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma |
title_short | Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma |
title_sort | targeting the sox2 parp1 complex to intervene in the growth of esophageal squamous cell carcinoma |
topic | Esophageal squamous cell carcinoma SOX2 PARP1 3-ABA Metformin |
url | http://www.sciencedirect.com/science/article/pii/S0753332222006989 |
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