PFKFB3 Control of Cancer Growth by Responding to Circadian Clock Outputs

Lili Chen, Jiajia Zhao, Qingming Tang, Honggui Li, Chenguang Zhang, Ran Yu, Yan Zhao, Yuqing Huo, Chaodong Wu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Circadian clock dysregulation promotes cancer growth. Here we show that PFKFB3, the gene that encodes for inducible 6-phosphofructo-2-kinase as an essential supporting enzyme of cancer cell survival through stimulating glycolysis, mediates circadian control of carcinogenesis. In patients with tongue cancers, PFKFB3 expression in both cancers and its surrounding tissues was increased significantly compared with that in the control, and was accompanied with dys-regulated expression of core circadian genes. In the in vitro systems, SCC9 tongue cancer cells displayed rhythmic expression of PFKFB3 and CLOCK that was distinct from control KC cells. Furthermore, PFKFB3 expression in SCC9 cells was stimulated by CLOCK through binding and enhancing the transcription activity of PFKFB3 promoter. Inhibition of PFKFB3 at zeitgeber time 7 (ZT7), but not at ZT19 caused significant decreases in lactate production and in cell proliferation. Consistently, PFKFB3 inhibition in mice at circadian time (CT) 7, but not CT19 significantly reduced the growth of implanted neoplasms. Taken together, these findings demonstrate PFKFB3 as a mediator of circadian control of cancer growth, thereby highlighting the importance of time-based PFKFB3 inhibition in cancer treatment.

Original languageEnglish (US)
Article number24324
JournalScientific Reports
Volume6
DOIs
StatePublished - Apr 15 2016

ASJC Scopus subject areas

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    Chen, L., Zhao, J., Tang, Q., Li, H., Zhang, C., Yu, R., Zhao, Y., Huo, Y., & Wu, C. (2016). PFKFB3 Control of Cancer Growth by Responding to Circadian Clock Outputs. Scientific Reports, 6, [24324]. https://doi.org/10.1038/srep24324