Progress in the role of DBF4-dependent kinase in tumor development and treatment

doi:10.3877/cma.j.issn.2095-1221.2024.01.009

Abstract

Abstract:

DBF4-dependent kinase (DDK) is formed by the binding of DBF4 and CDC7, and it could activate helicase. This activation plays a crucial role in cell replication. DBF4, as a regulatory subunit, also activates cell cycle kinases directly or indirectly by interacting with other proteins. This interaction further regulates the cell cycle process. It has been shown that the DBF4 gene is continuously overexpressed in many tumors. The overexpression of DBF4 leads to DDK kinase activation, which might be the underlying reason for cancer development. Targeted inhibition of DDK potentially inhibits tumor growth. Therefore, this article provides a comprehensive review on the structure and regulatory function of DDK, the role of DDK in tumor development, and the application of DDK inhibitors in tumor treatment, in order to provide a theoretical basis for the development of targeted tumor cell cycle therapy methods.

Key words: DBF4, DBF4-dependent kinase, CDC7, DDK inhibitors

Liuyan Chen, Yaoyao Liang, Jin Chen. Progress in the role of DBF4-dependent kinase in tumor development and treatment[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(01): 56-61.

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时间（年）	疾病	机制	DBF4的变化	结果
2007^[36]	皮肤黑色素瘤	/	DBF4上调	促进细胞周期进程，促进瘤的发展和预后
2017^[30]	肺腺癌	RB1-E2F和p53肿瘤抑制通路的失调	DDK表达增加，DBF4上调	促进肿瘤的化疗耐药性和生存
2020^[39]	多发性骨髓瘤	CDC7-DBF4抑制剂	DBF4下调	抑制细胞周期进程
2021^[29]	肺鳞状细胞癌	miR-30d-5p靶向DBF4	DBF4下调	抑制增殖、迁移、侵袭
2022^[27]	乳腺癌小鼠模型	激活MAPK通路	DBF4上调	促进细胞周期进程
2022^[40]	宫颈内膜癌	P53失活	DBF4上调	促进细胞周期进程
2022^[33]	肉瘤	靶向DBF4	DBF4下调	抑制细胞周期进程
2022^[34]	尤因肉瘤	CDC7-DBF4抑制剂治疗		抑制细胞周期进程
2022^[41]	RB阳性癌细胞	CDC7-DBF4抑制剂治疗CDK2-RB-E2F通路	DBF4下调	抑制细胞周期进程
2023^[24]	原发性肝癌	上游：p65诱导DBF4，下游：XPO1-STAT3通路	DBF4上调	促进增殖和肿瘤发生

时间（年）	疾病	机制	DBF4的变化	结果
2007^[36]	皮肤黑色素瘤	/	DBF4上调	促进细胞周期进程，促进瘤的发展和预后
2017^[30]	肺腺癌	RB1-E2F和p53肿瘤抑制通路的失调	DDK表达增加，DBF4上调	促进肿瘤的化疗耐药性和生存
2020^[39]	多发性骨髓瘤	CDC7-DBF4抑制剂	DBF4下调	抑制细胞周期进程
2021^[29]	肺鳞状细胞癌	miR-30d-5p靶向DBF4	DBF4下调	抑制增殖、迁移、侵袭
2022^[27]	乳腺癌小鼠模型	激活MAPK通路	DBF4上调	促进细胞周期进程
2022^[40]	宫颈内膜癌	P53失活	DBF4上调	促进细胞周期进程
2022^[33]	肉瘤	靶向DBF4	DBF4下调	抑制细胞周期进程
2022^[34]	尤因肉瘤	CDC7-DBF4抑制剂治疗		抑制细胞周期进程
2022^[41]	RB阳性癌细胞	CDC7-DBF4抑制剂治疗CDK2-RB-E2F通路	DBF4下调	抑制细胞周期进程
2023^[24]	原发性肝癌	上游：p65诱导DBF4，下游：XPO1-STAT3通路	DBF4上调	促进增殖和肿瘤发生

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