Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma

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

Biomedicine & Pharmacotherapy (Sep 2022)

Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma

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

Affiliations

Zhuo Wang: 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
Junkai Wang: Central Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China
Hongzhou Zhao: 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
Tingting Zhao: 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
Yunyun Chen: 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
Ming Jiang: Department of Gastroenterology of The Children's Hospital, Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
Shihui Zhang: Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4UU, UK
Yuxuan Wei: 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
Jiaying Zhang: School of Life Science, Xiamen University, Xiamen, Fujian 361102, China
Yijian Zhou: 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
Songlin Shi: School of Medicine, Xiamen University, Xiamen, Fujian 361102, China
Zhichao Fu: Department of radiotherapy, 900 Hospital of the Joint Logistics Team (Dongfang Hospital, Xiamen University), Fuzhou, Fujian 350025, China
Yaxin Yang: Department of Biology, University of Rochester, NY 14627, USA
Yujun Zhang: School of Medicine, Xiamen University, Xiamen, Fujian 361102, China
Ling Yang: School of Medicine, Xiamen University, Xiamen, Fujian 361102, China
Jianwen Que: Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Correspondence to: Department of Medicine, Columbia University, Medical Centre, USA.
Kuancan Liu: 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.

Journal volume & issue: Vol. 153
p. 113309

Abstract

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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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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