Background: CCN growth factor family regulates a variety of biological events such as cell proliferation, cell invasion, cell differentiation, apoptosis, and growth inhibition. Cysteine-rich protein 61 (Cyr61) is one of six secreted proteins in the CCNs. It has been shown that Cyr61 plays an important role in tumorigenesis and carcinogenesis in glioma, breast cancer, and gastric cancer, and others. However, Cyr61 has not yet been elucidated on the tumorigenesis, proliferation, and invasion of hepatocellular carcinoma, and needs to be researched and discovered. In this study, the HGF-mediated association of Cyr61, interleukin-8 (IL-8), and NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and cancer cell proliferation and invasion were investigated in two types of hepatoma cell lines. Methods: In this study, cell culture, cDNA microarray analysis, western blotting, Real-time Polymerase chain reaction, Zymography, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Cyr61 knock-down with short hairpin RNA (shRNA), chromatin immunoprecipitation assay, Standard two chamber invasion assay. Results: First, we confirmed that the expression level of Cyr61 was up-regulated by HGF (hepatocyte growth factor) in hepatoma cells. To identify associated pathway of HGF-induced Cyr61 about IL-8, NF-κB expression, the cells were treated with PI3K (Phosphoinositide 3-kinase) inhibitor (LY294002) and then analyzed by Western blotting. The HGF-mediated IL-8 and NF-κB levels were decreased with LY294002. The role for Cyr61 associated with IL-8 and NF-κB was determined by knock down cell of Cyr61. Cyr61-sh RNA cells showed a decreased level of IL-8 and NF-κB. HGF-mediated cell proliferation and invasion were decreased in Cyr61 knock down cell. Conclusions: These results suggest that Cry61 plays an important role in cell proliferation and metastasis in hepatocellular carcinoma, and Cry61 may be a novel target for the prevention of progression and treatment of hepatocellular carcinoma. Citation Format: Jiyoon Jung, sungae Koh, Kyunghee Lee, Jaeryong Kim. The cysteine rich protein 61 (Cyr61) contributes to tumor proliferation and invasion via HGF (hepatocyte growth factor) mediated NFkB signaling pathway in human hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB541.

Background: FOXA1 and FOXA2, members of the forkhead transcription factor family, are critical for epithelial differentiation in many endoderm-derived organs and important regulators in body homeostasis. It has been shown that FOXA2 plays an important role in tumorigenesis and carcinogenesis in glioma, breast cancer, hepatoma, and others. However, FOXA2 has not yet been elucidated on the tumorigenesis, proliferation, and invasion of human gastric cancer, and needs to be researched and discovered. In this study, the HGF-mediated association of FOXA2, extracellular signal-regulated protein kinase (ERK), and matrix metalloproteinase 9 (MMP9) and cancer cell proliferation and invasion were investigated in two types of human gastric cancer cell lines. Methods: In this study, cell culture, cDNA microarray analysis, western blotting, Real-time Polymerase chain reaction, Zymography, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, FOXA2 knock-down with short hairpin RNA (shRNA), chromatin immunoprecipitation assay, Standard two chamber invasion assay. Results: First, we confirmed that the expression level of FOXA2 was up-regulated by HGF (hepatocyte growth factor) in human gastric cancer cells. To identify the associated pathway of HGF-induced FOXA2 about ERK, MMP9 expression, the cells were treated with PI3K (Phosphoinositide 3-kinase) inhibitor (LY294002) and then analyzed by Western blotting. The role of FOXA2 associated with MMP9 and ERK was determined by knockdown cell of FOXA2. FOXA2-sh RNA cells showed a decreased level of MMP9 and ERK. HGF-mediated cell proliferation and invasion were decreased in FOXA2 knockdown cell. Conclusions: These results suggest that FOXA2 plays an important role in cell proliferation and metastasis in hepatocellular carcinoma, and FOXA2 may be a novel target for the prevention of progression and treatment of human gastric cancer. Citation Format: Jiyoon Jung, Sungae Koh, Kyunghee Lee. The FOXA2 contributes to tumor proliferation and invasion via HGF mediated ERK signaling pathway in human gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1488.

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Background: 14-3-3 protein family have many diverse functions in cellular responses including cell cycle regulation, apoptosis and malignant transformation in a broad range of organisms. 14-3-3 sigma induces G2 arrest enabling the repair of damaged DNA. Especially 14-3-3 sigma is frequently lost in tumor cells and surrounding tissues, indicate that becomes lost at an early stage in invasive cancer. The purpose of this study is to identify the role of HGF upregulated 14-3-3 sigma associated with cancer cell proliferation and invasion in gastric cancer and to identify the role of 14-3-3 sigma level in vivo by analysis 14-3-3 serum level in gastric cancer patients who underwent gastrectomy. Methods: In our study we used cell culture, Northern blotting, cDNA microarray analysis, western blotting, RT-PCR, Zymography, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 14-3-3 sigma knock-down with short hairpin RNA (shRNA), electrophoresis mobility-shift assay, chromatin immunoprecipitation assay, Standard two chamber invasion assay. And we conducted the 14-3-3 sigma ELISA (enzyme-linked immunosorbent assay) of 37 blood samples of patients, who underwent gastrectomy for gastric cancer. Results: First, we confirmed that the expression level of 14-3-3 sigma was up-regulated by HGF(hepatocyte growth factor) in gastric cancer cell. To identify associated pathway of HGF-induced 14-3-3 sigma about MMP-1 (matrix metalloproteinase-1) expression, the cells were treated with MEK (Mitogen-activated protein kinase kinase) inhibitor(PD098059) and then analyzed by Western blotting. The HGF-mediated MMP-1 protein level was decreased with PD098059. The role for 14-3-3 sigma associated with MMP-1 was determined by knock down cell of 14-3-3 sigma. 14-3-3 sigma-sh RNA cells showed a decreased level of MMP-1, pERK and pp38. HGF-mediated cell proliferation and in vitro invasion was decreased in 14-3-3 sigma knock down cell. We also identified that 14-3-3 sigma serum level was statistically significant decreased after gastrectomy in gastric cancer patients with stage 2 or 3. (p value < 0.05) Conclusions: Our results support the hypothesis that 14-3-3 sigma plays an important role in the cell proliferation in gastric cancer, and knock down this domain, it can be preventing to gastric cancer progression. And 14-3-3 sigma serum level is associated with status of treatment locally advanced gastric cancer. Citation Format: Jiyoon Jung, Kyunghee Lee, sungae Koh, sangwoon Kim. The significant role of 14-3-3 sigma including signal transduction, cell cycle regulation, and malignant transformation in human gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-031.