FOXM1 Promotes Malignant Proliferation of Esophageal Squamous Cell Carcinoma Through Transcriptional Activating CDC6.

Abstract

Forkhead box M1 (FOXM1) is a proliferative transcription factor and plays a vital role in many cancers. However, the function and molecular mechanism of FOXM1 in esophageal squamous cell carcinoma (ESCC) remain poorly understood. Hence, we aim to clarify the molecular basis of FOXM1-mediated ESCC progression. In this study, bioinformatics analysis showed that FOXM1 was mainly involved in key signal pathways, including cell proliferation, cell cycle, and homologous recombination in ESCC, and predicted that CDC6 might be a potential regulatory target gene of FOXM1. The results revealed that FOXM1 and CDC6 were significantly overexpressed in ESCC tissue and cell line, and their expression was positively correlated. Further studies showed that FOXM1 directly transcriptionally activated CDC6 by binding to its promoter region in ESCC cells. Moreover, FOXM1 mediated ESCC cell proliferation by regulating CDC6 expression, which may be related to promoting G1-S phase transition of cell cycle. Taken together, FOXM1-CDC6 axis mediates ESCC malignant proliferation and may serve as a potential biological target for ESCC treatment.