title: Decreased FOXF1 promotes hepatocellular carcinoma tumorigenesis, invasion, and stemness and is associated with poor clinical outcome.
abstract: Forkhead box F1 (FOXF1), a member of the forkhead transcription factor superfamily, plays critical roles in the progression of certain types of cancers. However, the expression and function of FOXF1 in human hepatocellular carcinoma (HCC) are still unclear. Quantitative real-time reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry detected the relatively lower expression status of FOXF1 in HCC cases. Soft agar and transwell assays clearly demonstrated that FOXF1-knockdown cells showed significantly increased in vitro cell tumorigenesis and invasion, and FOXF1-overexpressing cells had significantly reduced growth and invasion potential. Our study also examined the role of FOXF1 in HCC cell stemness by sphere formation, aldehyde dehydrogenase (ALDH1) activity, and CD44/133-positive cell analysis. Enforced FOXF1 expression decreased HCC cell stemness, and the downregulation of FOXF1 promoted cancer cell stemness. The in vivo study showed that overexpressed FOXF1 inhibits nude mouse tumorigenicity with downregulation of CD44 and proliferating cell nuclear antigen. More importantly, loss of FOXF1 expression was linked to poor overall survival time by Kaplan-Meier analysis.
authors.affiliation: Department of Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China; Department of General Surgery, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, People's Republic of China.
authors.forename: Zhen-Guo
authors.initials: ZG
authors.lastname: Zhao
authors.affiliation: Tumor Treatment Center, The Affiliated Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: De-Qiang
authors.initials: DQ
authors.lastname: Wang
authors.affiliation: Clinical Laboratory, The Second People's Hospital of Huai'an, Huai'an, People's Republic of China.
authors.forename: De-Fei
authors.initials: DF
authors.lastname: Hu
authors.affiliation: Department of Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: You-Sheng
authors.initials: YS
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, People's Republic of China.
authors.forename: Shuang-Hai
authors.initials: SH
authors.lastname: Liu
keywords: FOXF1; cancer stemness; clinical outcome; hepatocellular carcinoma; invasion; tumorigenesis