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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2022-09-01
Series:Biomedicine & Pharmacotherapy
Subjects:
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.
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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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