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

doi:10.1016/j.biopha.2022.113309

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

Biomed Pharmacother. 2022 Sep:153:113309. doi: 10.1016/j.biopha.2022.113309. Epub 2022 Jun 20.

Authors

Zhuo Wang¹, Junkai Wang², Hongzhou Zhao¹, Tingting Zhao¹, Yunyun Chen¹, Ming Jiang³, Shihui Zhang⁴, Yuxuan Wei¹, Jiaying Zhang⁵, Yijian Zhou¹, Songlin Shi⁶, Zhichao Fu⁷, Yaxin Yang⁸, Yujun Zhang⁶, Ling Yang⁶, Jianwen Que⁹, Kuancan Liu¹⁰

Affiliations

¹ 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.
² Central Laboratory, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
³ Department of Gastroenterology of The Children's Hospital, Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
⁴ Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4UU, UK.
⁵ School of Life Science, Xiamen University, Xiamen, Fujian 361102, China.
⁶ School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
⁷ Department of radiotherapy, 900 Hospital of the Joint Logistics Team (Dongfang Hospital, Xiamen University), Fuzhou, Fujian 350025, China.
⁸ Department of Biology, University of Rochester, NY 14627, USA.
⁹ Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: jq2240@cumc.columbia.edu.
¹⁰ 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. Electronic address: liukuancan@163.com.

PMID: 35738180
DOI: 10.1016/j.biopha.2022.113309

Abstract

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.

Keywords: 3-ABA; Esophageal squamous cell carcinoma; Metformin; PARP1; SOX2.

MeSH terms

Cell Line, Tumor
Cell Proliferation
Esophageal Neoplasms* / genetics
Esophageal Squamous Cell Carcinoma* / genetics
Humans
Poly (ADP-Ribose) Polymerase-1* / genetics
SOXB1 Transcription Factors* / genetics

Substances

SOX2 protein, human
SOXB1 Transcription Factors
PARP1 protein, human
Poly (ADP-Ribose) Polymerase-1