American Association for Cancer Research
15357163mct181215-sup-211069_3_supp_5674933_pv5qdl.pptx (10.46 MB)

Supplementary Data from Inhibition of AKT Sensitizes Cancer Cells to Antineoplastic Drugs by Downregulating Flap Endonuclease 1

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posted on 2023-04-03, 16:09 authored by Hong Zhu, Congye Wu, Ting Wu, Wen Xia, Shusheng Ci, Weiru He, Yilan Zhang, Lulu Li, Shiying Zhou, Jing Zhang, Ashlin M. Edick, Anna Zhang, Fei-Yan Pan, Zhigang Hu, Lingfeng He, Zhigang Guo

Figure S1-S5


National Natural Science Foundation of China

Changzhou Sci and Tech Program

Jiangsu Key Research and Development Program

National Nature Science Foundation



DNA repair mechanisms are crucial for cell survival. It increases the cancer cell's ability to resist DNA damage. FEN1 is involved in DNA replication and repair, specifically long-patch base excision repair. Although the gene function and post-translational modification of FEN1 are well studied, the regulatory mechanism of FEN1 by upstream signal pathways remains unclear. In this article, we have identified AKT as a regulator of FEN1 activity in lung cancer cells. Sustained activation of AKT can phosphorylate nuclear transcription factor NF-κB/p65. NF-κB/p65 directly binds to FEN1 promoter to promote a high transcription level of FEN1, revealing the contribution of the AKT signaling pathway to drug resistance of cancer cells. The combination of an AKT inhibitor and cisplatin efficiently suppressed lung cancer cell growth both in vitro and in vivo. Our study illustrated an upstream regulatory mechanism of FEN1, which will contribute to the development of effective lung cancer therapies.These findings identified AKT as a regulator of FEN1 activity and revealed the AKT signaling pathway's contribution to drug resistance, which will contribute to the development of effective lung cancer therapy.

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