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Updated: Feb 11, 2026
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Cell division cycle 7 is a potential therapeutic target in oral squamous cell carcinoma and is regulated by E2F1
Shufang Jin1,2, Hailong Ma1,2, Wenyi Yang1,2
1Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, Shanghai, 200011, China.
Abstract:
Cell division cycle 7 (Cdc7) plays important roles in the regulation of the initiation of DNA replication throughout S phase. Whether inhibition of Cdc7 has a direct antitumour effect in oral squamous cell carcinoma (OSCC) remains unclear. In this study, XL413, a novel Cdc7 inhibitor, markedly inhibited the viability of OSCC cells but not that of non-tumour primary cells. There was a synergistic effect between XL413 and DNA-damaging agents (e.g. cisplatin and 5-fluorouracil) on OSCC in vitro and in vivo. Moreover, XL413 exhibited a notable antitumour effect on OSCC patients with high Cdc7 expression in mini patient-derived xenografts model. The proliferation was significantly inhibited in OSCC cells after Cdc7 silencing. Cdc7 knockdown significantly induced apoptosis in OSCC cell lines. Furthermore, we demonstrated that Cdc7 was overexpressed and transcriptionally regulated by E2F1 in OSCC by using chromatin immunoprecipitation and luciferase assays. Our results reveal that XL413 has an excellent antitumour effect in OSCC. Importantly, it does not inhibit the proliferation of non-tumour cells. These findings suggest that the overexpression of Cdc7 promotes progression in OSCC and that inhibition of Cdc7 is a very promising therapy for OSCC patients.
Insights
XL413, a Cdc7 inhibitor, effectively reduced oral squamous cell carcinoma (OSCC) cell viability and proliferation. This Cdc7 inhibition shows promise as a targeted therapy for OSCC, sparing non-tumour cells.
Area of Science:
- Molecular Biology
- Oncology
- Cancer Therapeutics
Background:
- Cell division cycle 7 (Cdc7) is crucial for DNA replication initiation during S phase.
- The role of Cdc7 inhibition in oral squamous cell carcinoma (OSCC) treatment is not well-defined.
Purpose of the Study:
- To investigate the direct anti-tumour effects of the novel Cdc7 inhibitor XL413 in OSCC.
- To explore the therapeutic potential of targeting Cdc7 in OSCC.
Main Methods:
- Treatment of OSCC cells and non-tumour cells with XL413.
- In vitro and in vivo studies assessing synergistic effects with DNA-damaging agents (cisplatin, 5-fluorouracil).
- Cdc7 knockdown experiments and analysis of proliferation and apoptosis.
- Chromatin immunoprecipitation and luciferase assays to determine Cdc7 regulation by E2F1.
Main Results:
- XL413 significantly inhibited OSCC cell viability and proliferation, with no effect on non-tumour cells.
- XL413 demonstrated synergistic anti-tumour effects with cisplatin and 5-fluorouracil in vitro and in vivo.
- Cdc7 knockdown induced apoptosis and inhibited proliferation in OSCC cells.
- Cdc7 was found to be overexpressed and transcriptionally regulated by E2F1 in OSCC.
Conclusions:
- XL413 exhibits potent anti-tumour activity against OSCC, highlighting Cdc7 as a therapeutic target.
- Cdc7 overexpression promotes OSCC progression.
- XL413 represents a promising therapeutic strategy for OSCC patients, particularly those with high Cdc7 expression.
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