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Updated: Sep 6, 2025
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma
Zhuo Wang1, Junkai Wang2, Hongzhou Zhao1
1Central 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.
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.
Insights
Targeting Poly(ADP-Ribose) polymerase 1 (PARP1), a SOX2 binding partner, can reduce esophageal squamous cell carcinoma (ESCC) proliferation. This approach may offer new therapeutic strategies for ESCC patients with elevated SOX2.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Elevated SOX2 protein levels are linked to increased esophageal squamous cell carcinoma (ESCC) incidence.
- SOX2 is a potential therapeutic target for ESCC, but effective treatments are still under investigation.
Purpose of the Study:
- To investigate the interaction between SOX2 and Poly(ADP-Ribose) polymerase 1 (PARP1) in ESCC.
- To evaluate the therapeutic potential of inhibiting PARP1 in ESCC treatment.
Main Methods:
- Utilized 3-aminobenzamide (3-ABA) and shRNA to inhibit PARP1 in ESCC cells.
- Performed RNA sequencing to analyze the effects of PARP1 inhibition on signaling pathways.
- Assessed the synergistic effects of 3-ABA in combination with cisplatin and metformin.
Main Results:
- PARP1 was found to interact with SOX2 in ESCC.
- PARP1 inhibition reduced ESCC cell proliferation and decreased SOX2 protein levels.
- PARP1 inhibition impacted multiple cancer cell proliferation pathways.
- 3-ABA showed synergistic effects with cisplatin and potentiated by metformin.
Conclusions:
- Targeting the SOX2 binding partner PARP1 is a potential therapeutic strategy for ESCC.
- Inhibiting PARP1 offers a promising avenue for treating ESCC patients with high SOX2 levels.
