Upregulation of Yes-associated protein and transcriptional co-activator with PDZ-binding motif influences the behavior of LOVO human colon adenocarcinoma cells

Abstract

Abstract. The present study aimed to investigate the role of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) in the LOVO human colon adenocarcinoma cell line and explore the underlying mechanisms. First, the expression levels of YAP and TAZ were detected in LOVO cells using reverse-transcription quantitative PCR, and the results suggested that YAP and TAZ were faintly expressed in LOVO cells. To investigate the exact role of YAP and TAZ in LOVO cells, stable YAP-and/or TAZ-overexpressing LOVO cell lines were established using YAP and/or TAZ expression plasmids. An MTT assay and flow cytometry were used to assess cell proliferation and apoptosis, respectively. The results indicated that compared with the control, YAP or TAZ overexpression significantly increased the proliferation ability of LOVO cells, while apoptosis was significantly decreased. Furthermore, the expression of the tumor-associated proteins connective tissue growth factor and cysteine-rich angiogenic inducer 61, which have critical roles in facilitating cancer cell proliferation, migration and invasion, were found to be upregulated following upregulation of YAP and TAZ. In addition, the expression of cell apoptosis-associated protein B-cell lymphoma 2 (Bcl-2) was significantly increased, while Bcl-2-associated X protein and caspase-3 were inhibited by YAP or TAZ overexpression. All of these effects were amplified when YAP and TAZ were co-overexpressed. In conclusion, YAP and TAZ function as tumor promoters in human colon carcinoma, and upregulation of YAP and TAZ influences the behavior of LOVO colon adenocarcinoma cells via regulating tumor-associated gene expression.

The Ambivalent Function of YAP in Apoptosis and Cancer

“…Moreover, silencing the expression of YAP gene by shRNA [18,32,33] or siRNA [15,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48] could induce apoptosis (Table 1). Consistent with this finding, overexpressing YAP significantly inhibited apoptosis of liver [38,49,50], pancreas [39], colorectal cancer [15,51], and lung cancer cells [52]. All these publications suggest that YAP inhibits apoptosis.…”

Context-dependent roles of YAP/TAZ in stem cell fates and cancer

“…Like during mESC differentiation, YAP primarily regulates apoptosis in cancer via transcriptional regulation of anti-and pro-apoptotic genes, most commonly BCL-2 and BAX. In colon adenocarcinoma, overexpression of YAP or TAZ reduces apoptosis via the upregulation of BCL-2 and downregulation of BAX; reducing YAP levels is sufficient to trigger apoptosis [153,154]. BAX is repressed by YAP in prostate cancer [155][156][157], and YAP, TEAD, and SLUG collaborate to directly repress pro-apoptotic BMF in dormant non-small cell lung cancer [158].…”