NCF2 drives tumor progression and metastasis through NR2F2/LATS2/YAP1 axis in esophageal squamous cell carcinoma

Abstract

The occurrence of lymph node spread is the major significant factor associated with esophageal squamous cell carcinoma (ESCC)'s poor prognosis, mainly because of its association with a high risk of recurrence after treatment. However, the biological mechanisms underlying lymphatic metastasis in ESCC are not well recognized. Here, we show that NCF2 is aberrantly overexpressed and is associated with poor prognosis in patients with ESCC. Dysregulation of NCF2 expression promotes ESCC progression and lymphatic metastasis in a ROS-independent manner. NCF2 directly interacts with NR2F2 and blocks its nuclear translocation, which can result in the downregulation of LATS2 and the activation of YAP1 and its target genes and thereby promote tumorigenesis, lymphangiogenesis and metastasis in ESCC. This study establishes that the NCF2/NR2F2/LATS2/YAP1 axis plays a vital role in tumorigenesis and metastasis, suggesting that NCF2 may serve as an attractive therapeutic target and prognostic marker in ESCC.