FEN1 promotes tumor progression and confers cisplatin resistance in non‐small‐cell lung cancer. Issue 6 (12th May 2017)

• Record Type: Journal Article
• Authors: He, Lingfeng; Luo, Libo; Zhu, Hong; Yang, Huan; Zhang, Yilan; Wu, Huan; Sun, Hongfang; Jiang, Feng; Kathera, Chandra S.; Liu, Lingjie; Zhuang, Ziheng; Chen, Haoyan; Pan, Feiyan; Hu, Zhigang; Zhang, Jing; Guo, Zhigang
• Is Part Of: Molecular oncology. Volume 11:Issue 6(2017)
• Page Start: 640
• Page End: 654
• Publication Date: 2017-05-12
• Subjects: cisplatin resistance -- flap endonuclease 1 -- lung cancer -- targeted therapy; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12058
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells. Suppression of FEN1 resulted in decreased DNA replication and accumulation of DNA damage, which subsequently induced apoptosis. Manipulating the amount of FEN1 altered the response of lung cancer cells to chemotherapeutic drugs. A small‐molecule inhibitor (C20) was used to target FEN1 and this enhanced the therapeutic effect of cisplatin. The FEN1 inhibitor significantly suppressed cell proliferation and induced DNA damage in lung cancer cells. In mouse models, the FEN1 inhibitor sensitized lung cancer cells to a DNA damage‐inducing agent and efficiently suppressed cancer progression in combination with cisplatin treatment. Our study suggests that targeting FEN1 may be a novel and efficient strategy for a tumor‐targeting therapy for lung cancer. Abstract : The resistance of lung cancer cells to chemotherapy is a major challenge. The DNA endonuclease FEN1 is involved in DNA repair and is overexpressed in lung cancer cells. In this study, we show that FEN1 plays a critical role in the rapid proliferation of non‐small lung cancer cells and contributes to cisplatin resistance. Targeting FEN1 may thus be a novel strategy for lung cancer therapy.