Abstract
Activation of YAP/TEAD signaling is very common in the progression of HCC (Hepatocellular carcinoma). Nuclear pore complex (NPC) regulates the shuttling of proteins between cytoplasm and nucleus. Nuclear accumulation of YAP protein has been observed in the majority of HCC tissues. However, whether NPC could regulate the YAP/TEAD signaling remains unknown. In this study, it was found NUP37, the component of NPC, significantly up-regulated in HCC clinical samples and mouse model. Over-expression of NUP37 promoted the growth, migration and invasion of HCC cells, while knocking down the expression of NUP37 inhibited the growth, migration, invasion and metastasis of HCC cells and improved the survival of the mouse model. NUP37 interacted with YAP and activated YAP/TEAD signaling by enhancing the interaction between YAP and TEAD. Taken together, these data demonstrated the oncogenic roles of NUP37 in the progression of HCC and suggested that NUP37 might be a promising therapeutic target.
Highlights
Hepatocellular carcinoma (HCC), a malignancy with poor survival, is prevalent in Asia contries, especially China
Low expression of NUP37 was observed in the normal liver cell line (LO2) and high expression of NUP37 was observed in HCC cell line (PVTT, Hep3B, MHCC97, 7404, Huh-7 and QGY) (Figure 1E)
Whether Nuclear pore complex (NPC) regulated the YAP/TEAD signaling in HCC remains unknown
Summary
Hepatocellular carcinoma (HCC), a malignancy with poor survival, is prevalent in Asia contries, especially China. Several studies have demonstrated that activation of YAP/TEAD signaling promoted the development of HCC [4, 5]. YAP (Yes-associated protein) is the key component of Hippo signaling which controls the sizes of the organs [6]. Hippo kinases MST1/2 tightly control the location and protein level of YAP by promoting its phosphorylation and degradation [7]. It has been demonstrated that high density of the cell culture activated the kinase activity of MST1/2 and led to the cytoplasmic localization of YAP [6]. Due to loss function of upstream regulator, YAP was accumulated in the nucleus where it formed a complex with TEAD and activated a panel of growthrelated and growth-relate genes, such as CYR61, CTGF and Cyclin E [6, 8] The shuttle of YAP from the cytoplasm to the nucleus through nuclear pore complex (NPC) is essential for its oncogenic roles. Whether the NPC regulates YAP/TEAD signaling remains unknown
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