Open AccessFEN 1 promotes tumor progression and confers cisplatin resistance in non‐small‐cell lung cancer
Author(s) -
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
Publication year - 2017
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12058
Subject(s) - cisplatin , lung cancer , dna repair , cancer research , dna damage , cancer , cancer cell , biology , apoptosis , base excision repair , cell growth , chemotherapy , medicine , dna , pathology , genetics
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 ( FEN 1) is overexpressed in lung cancer cells. FEN 1 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 FEN 1 is critical for the rapid proliferation of lung cancer cells. Suppression of FEN 1 resulted in decreased DNA replication and accumulation of DNA damage, which subsequently induced apoptosis. Manipulating the amount of FEN 1 altered the response of lung cancer cells to chemotherapeutic drugs. A small‐molecule inhibitor (C20) was used to target FEN 1 and this enhanced the therapeutic effect of cisplatin. The FEN 1 inhibitor significantly suppressed cell proliferation and induced DNA damage in lung cancer cells. In mouse models, the FEN 1 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 FEN 1 may be a novel and efficient strategy for a tumor‐targeting therapy for lung cancer.