<p>Targeting Yes1 Associated Transcriptional Regulator Inhibits Hepatocellular Carcinoma Progression and Improves Sensitivity to Sorafenib: An in vitro and in vivo Study</p>

Abstract

Purpose The aim of this study was to investigate the role of Yes1 associated transcriptional regulator (YAP1) in the pathology of hepatocellular carcinoma (HCC) and its potential as a therapeutic target. Methods YAP1 expression in HCC and adjacent tissues was determined via immunohistochemistry; in HCC and human normal liver cell lines, expression was examined via Western blotting. The effects of YAP1 knockdown and overexpression were detected following transfection of HCC cells with siRNA-YAP1 recombinants or pcDNA3.1-YAP1 plasmids. A tumor xenograft model was constructed by implanting YAP1-knockdown lentivirus-infected Hep-3B cells into nude mice, and the animals were treated with sorafenib. Results In patients with HCC, YAP1 was upregulated in tumor tissue compared with adjacent tissue, and its high expression in the tumor was associated with increased Edmonson grade. In vitro, YAP1 expression was increased in Hep-3B, SK-HEP-1 and Huh7 cells, while it was similar in SMMC-7721 cells and LO2 cells. Meanwhile, YAP1 increased cell proliferation and invasion, promoted the progression of epithelial–mesenchymal transition, and inhibited cell apoptosis in HCC cells; furthermore, YAP1 knockdown combined with the administration of sorafenib decreased cell viability and increased cell apoptosis compared with YAP1 knockdown or treatment with sorafenib alone. In vivo, YAP1 knockdown inhibited tumor growth and metastasis, whereas it promoted apoptosis; meanwhile, YAP1 knockdown synergized with sorafenib to suppress tumor progression in HCC mice. Conclusion YAP1 is upregulated in both HCC tumor tissues and cell lines. Moreover, it promotes cell proliferation and invasion and promoted the progression of epithelial–mesenchymal transition in vitro. Furthermore, targeting YAP1 inhibits HCC progression and improves sensitivity to sorafenib in vitro and in vivo.

Transcription factor glucocorticoid modulatory element-binding protein 1 promotes hepatocellular carcinoma progression by activating Yes-associate protein 1

“…The increase in YAP1 expression is connected with the poor prognosis of BC patients, and inhibits PTEN expression to boost BC cell multiplication and repress the apoptosis[ 44 ]. In HCC, YAP1 can facilitate cell proliferation, invasion and EMT process in vitro [ 45 ]. In our study, we first found that GMEB1 could bind with the YAP1 promoter region and could positively modulate YAP1 expression in HCC cells.…”

Cancer Cell-Intrinsic Alterations Associated with an Immunosuppressive Tumor Microenvironment and Resistance to Immunotherapy in Lung Cancer

“…This family plays an important role in the activation of prosurvival signaling pathways, migration and invasion [ 145 ]. Many studies have evidenced the protumorigenic activity of YES1 in a wide variety of solid tumors, such as breast cancer [ 146 ], prostate cancer [ 147 ], gastric cancer [ 148 ], liver cancer [ 149 ], NSCLC [ 150 ] and SCLC [ 151 ], among others. In NSCLC, YES1 gene amplification was found in 15% of LUADs and 25% of LUSCs, with a significant positive correlation between YES1 gene copy number and mRNA expression [ 150 ].…”