OncoTargets and Therapy (Dec 2018)
Targeting CDC7 improves sensitivity to chemotherapy of esophageal squamous cell carcinoma
Abstract
Ji-Xiang Cao,1,2,* Yao Lu3,*1Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Science, Peking University, Beijing 100871, People’s Republic of China; 2Department of Pathology, Zhongshan Hospital Xiamen University, Xiamen 361004, People’s Republic of China; 3Department of Rehabilitation Medicine, Peking University 3rd Hospital, Beijing 100191, People’s Republic of China*Both authors contributed equally to this workPurpose: The cell division cycle 7 (CDC7) is a serine/threonine kinase that is essential for DNA replication in human cells which has been identified to play a critical role in multiple cancer types. However, the expression and clinical significance of CDC7 in ESCC has never been reported.Patients and methods: CDC7 expression was detected in 30 ESCC and matched adjacent normal tissues, and a series of loss-of-function and gain-of-function assays were performed to evaluate the effects of CDC7 on the proliferation, migration and invasion, and chemoresistance of ESCC cells.Results: The results showed that CDC7 was highly expressed in ESCC tissues compared with matched adjacent normal tissues. Functional studies demonstrated that knockdown of CDC7 inhibited proliferation by arresting ESCC cells in the G0/G1 phase and inducing apoptosis. Knockdown of CDC7 also inhibited cell migration and invasion in ESCC cells. Furthermore, knockdown of CDC7 sensitized ESCC cells to Cis and 5-FU.Conclusion: Our results suggest that CDC7 is highly expressed in ESCC tissues, and silencing CDC7 enhances chemosensitivity of ESCC cells, providing a new avenue for ESCC therapy.Keywords: CDC7, ESCC, chemosensitivity, therapeutic target, proliferation, migration and invasion
