Exo70 is transcriptionally up-regulated by hepatic nuclear factor 4α and contributes to cell cycle control in hepatoma cells

Abstract

Exo70, a member of the exocyst complex, is involved in cell exocytosis, migration, invasion and autophagy. However, the expression regulation and function of Exo70 in hepatocellular carcinoma are still poorly understood. In this study, we found Exo70 expression in human hepatoma cells was greatly reduced after knocking down hepatic nuclear factor 4α (HNF4α), the most important and abundant transcription factor in liver. This regulation occurred at the transcriptional level but not post-translational level. HNF4α transactivated Exo70 promoter through directly binding to the HNF4α-response element in this promoter. Cell cycle analysis further revealed that down-regulation of HNF4α and Exo70 was essential to berberine-stimulated G2/M cell cycle arrest in hepatoma cells. Moreover, knocking down either Exo70 or HNF4α induced G2/M phase arrest of hepatoma cells. Exo70 acted downstream of HNF4α to stimulate G2/M transition via increasing Cdc2 expression. Together, our results identify Exo70 as a novel transcriptional target of HNF4α to promote cell cycle progression in hepatoma, thus provide a basis for the development of therapeutic strategies for hepatocellular carcinoma.

Exo70 is an independent prognostic factor in colon cancer

“…Knockdown of Exo70 in MDA-MB-231 cells abolished the secretion of MMPs, whereas the overexpression of Exo70 promoted MMP secretion 22 . From HeLa cells and MDA-MB-231 cells, Exo70 directly interacts with the Arp2/3 complex, a core nucleating factor for the generation of branched actin networks for cell morphogenesis and migration 21 . And this interaction is important for the regulation of actin assembly at the leading edge of migrating cells 16 .…”

Deregulation of Exo70 Facilitates Innate and Acquired Cisplatin Resistance in Epithelial Ovarian Cancer by Promoting Cisplatin Efflux

“…Exo70 is also reported to accelerate polarized lysosome secretion at the immune synapse and promote cell migration and invasion in multiple types of tumors [22][23][24][25][26]. In previous studies, we reported that Exo70 affects the progression of liver cancer and breast cancer [27,28]. However, it remains to be seen whether Exo70 is involved in the tumorigenesis, progression, or platinum resistance of EOC.…”

Berberine: A novel therapeutic strategy for cancer

“…Pyroptosis is a programmed cell death based on caspase-1. 99,100 According to an investigation, BBR (20 μg/ml) induced cell cycle arrest in the G0/G1 phase in T-ALL Jurkat cells. 101 It was also revealed that BBR induced G1 arrest and apoptosis by increasing p27Kip1 and decreasing Cyclin D, Cyclin E, CDK2, and CDK4 in glioblastoma cells.…”