14-3-3ɛ functions as an oncogene in SGC7901 gastric cancer cells through involvement of cyclin E and p27kip1

Abstract

Investigation into the highly conserved 14‑3‑3ε protein has become increasingly important in cell biology due to its involvement in cell survival signaling, cell cycle control and apoptosis. The 14‑3‑3ε protein has been found to exert an impact on the development of various tumor types. However, the functional role and the possible mechanism of 14‑3‑3ε in gastric cancer remains to be elucidated. A previous study by our group indicated a negative correlation between 14‑3‑3ε expression levels and gastric cancer tissue differentiation and a positive correlation between 14‑3‑3ε expression levels and tumor infiltration, lymph node metastasis and tumor, nodes and metastasis staging. In the present study, 14‑3‑3ε suppression in the SGC7901 gastric cancer cell line was demonstrated to inhibit cell proliferation in vitro and tumor growth in vivo and the cell cycle‑associated proteins cyclin E and p27kip1 may have contributed to this antitumor effect. The present study showed for the first time that reducing the expression of 14‑3‑3ε may inhibit the proliferation and progression of gastric cancer and inhibition of this protein may provide a potential strategy for gastric cancer therapy in the future.

Proteomic analysis of cell cycle arrest and differentiation induction caused by ATPR, a derivative of all‐trans retinoic acid, in human gastric cancer SGC‐7901 cells

“…It has also been proposed to be a candidate tumor promoter or biomarker in some cancers. For gastric cancer, 14‑3‑3ε suppression in the SGC‐7901 gastric cancer cell line was demonstrated to inhibit cell proliferation in vitro and tumor growth in vivo, and the cell cycle‑associated proteins cyclin E and P27kip1 may have contributed to this antitumor effect . Cyclin E and P27kip1 are important cell cycle regulatory proteins whose expression is mediated by the FOXO signaling pathway.…”

Integrative Role of 14-3-3ε in Sleep Regulation

“…14-3-3 proteins are found to be important in both cancer- and age-related neurodegenerative disease [ 40 ], which can directly interact with yki [ 17 ], an important cancer factor in the Hippo pathway [ 19 , 40 ]. Previous studies indicated that 14-3-3ε is involved in gastric cancer and colorectal cancer [ 41 , 42 , 43 , 44 , 45 , 46 ], and disrupted sleep is a risk factor that contributes to cancer [ 47 ]. Many current papers showed a link between molecules upregulated in cancer patients and selected sleep disturbances.…”

“…In this current study, we found that 14-3-3ε, controlled by Clock, regulates sleep through pathways of both the 14-3-3ε/Ubx/PDF and neurotransmitters. In addition, there are previous reports that 14-3-3ε is also related to cancers [ 40 , 41 , 42 , 43 , 44 , 45 , 46 ], indicating that 14-3-3ε is a multifunctional gene in Drosophila regulating different physiological activities. Currently, the direct relationship between cancer and sleep is still unclear, which need to be carefully designed for systematical investigation in future.…”

Arsenic trioxide enhances the chemotherapeutic efficiency of cisplatin in cholangiocarcinoma cells via inhibiting the 14-3-3ε-mediated survival mechanism

“…14-3-3ɛ had an irreplaceable role in HCC, for mechanisms, it contributed to promote cell migration via the activation of the NF-κB/ FAK pathway and also stimulate EMT in HCC by suppressing E-cadherin via Zeb-1 21,22 . As for gastric cancer, 14-3-3ɛ might participate in the expression of cyclins binding to CDKs, and then degrading phosphorylated p27 kip1 to regulate the proliferation and progression of gastric cancer 20 . Thus, phosphorylation regulation brings into play the essential role in the function of 14-3-3ɛ.…”

“…2b). Increasing evidence suggested that 14-3-3ε isoform had become critical in cell biology due to its functions in carcinogenesis and tumor progression 19,20 . Especially, in hepatocellular carcinoma, 14-3-3ɛ had an irreplaceable tumor-promoting role 21,22 .…”