Lentiviral vector-mediated siRNA knockdown of the YAP gene inhibits growth and induces apoptosis in the SGC7901 gastric cancer cell line

Zhou, Zhou; Zhu, Jingde; Xu, Zhipeng; Zhang, Qiang

doi:10.3892/mmr.2011.543

Cited by 22 publications

(30 citation statements)

References 28 publications

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“…Based on the high levels of conservation between Drosophila Yki and Dac and their human counterparts, our work suggests that mammalian DACH proteins might also inactivate the transcriptional activity of YAP and/or TAZ (also known as WWTR1) on a subset of target genes by interacting with specific YAP or TAZ DNA-binding partners. In agreement with this possibility, DACH1 and YAP or TAZ regulate cyclin D1 expression (Wu et al, , 2007Zhou et al, 2011). Therefore, we propose that oncogenic transformation associated with increased YAP or TAZ transcriptional activity could result not only from perturbation of YAP or TAZ localization or levels (Pan, 2010), but also from inactivation of the tissue-specific DACH co-repressors.…”

Section: Dac or Dachs And Cancersupporting

confidence: 49%

The retinal determination genedachshundrestricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex

2015

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The Drosophila transcriptional co-activator protein Yorkie and its vertebrate orthologs YAP and TAZ are potent oncogenes, whose activity is normally kept in check by the upstream Hippo kinase module. Upon its translocation into the nucleus, Yorkie forms complexes with several tissue-specific DNA-binding partners, which help to define the tissue-specific target genes of Yorkie. In the progenitor cells of the eye imaginal disc, the DNA-binding transcription factor Homothorax is required for Yorkie-promoted proliferation and survival through regulation of the bantam microRNA (miRNA). The transit from proliferating progenitors to cell cycle quiescent precursors is associated with the progressive loss of Homothorax and gain of Dachshund, a nuclear protein related to the Sno/Ski family of co-repressors. We have identified Dachshund as an inhibitor of Homothorax-Yorkie-mediated cell proliferation. Loss of dachshund induces Yorkie-dependent tissue overgrowth. Conversely, overexpressing dachshund inhibits tissue growth, prevents Yorkie or Homothorax-mediated cell proliferation of disc epithelia and restricts the transcriptional activity of the YorkieHomothorax complex on the bantam enhancer in Drosophila cells. In addition, Dachshund collaborates with the Decapentaplegic receptor Thickveins to repress Homothorax and Cyclin B expression in quiescent precursors. The antagonistic roles of Homothorax and Dachshund in Yorkie activity, together with their mutual repression, ensure that progenitor and precursor cells are under distinct proliferation regimes. Based on the crucial role of the human dachshund homolog DACH1 in tumorigenesis, our work suggests that DACH1 might prevent cellular transformation by limiting the oncogenic activity of YAP and/or TAZ.

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Section: Dac or Dachs And Cancersupporting

confidence: 49%

The retinal determination genedachshundrestricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex

2015

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“…MMP-2 is thought to be a key enzyme involved in the degradation of type IV collagen, and a high level of MMP-2 in tissues is associated with tumor growth and invasion (24). It has been reported that YAP knockdown significantly increases the GO/G1 cell population and reduces expression levels of a number of genes crucial to cell proliferation and apoptosis, including Ki-67, PCNA, survivin and cyclin 01 (25). However, little has been reported on the effect ofYAP on MMP-2 expression.…”

Section: Effect Of Knockdown Of Yap On Gastric Cancer Cell Metastasismentioning

confidence: 99%

Expression and Yes-Associated Protein in Gastric Adenocarcinoma and Inhibitory Effects of its Knockdown on Gastric Cancer Cell Proliferation and Metastasis

Zhang

Yang

et al. 2012

Int J Immunopathol Pharmacol

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Yes-associated protein (YAP) has been implicated as an oncogene in multiple human cancers. In the present study, human gastric adenocarcinoma tissues of different grades (N=78) were collected and the mRNA and protein expression of YAP and phosphorylated YAP (p-YAP) in gastric adenocarcinomas were evaluated using immunohistochemistry, Real-time PCR and Western blot assays. Then, human gastric cancer SGC-7901 cells were stably transfected with lentivirus-mediated YAP small hairpin RNA (shRNA). The expression levels ofYAP,proliferating cell nuclear antigen (PCNA) and metalloproteinase-2 (MMP-2) were detected and the effects of shRNA-mediated knockdown ofYAP on cell proliferation and metastasis were assessed in gastric cancer cells. As a result, the expression ofYAP was observed in 69.23% gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Knockdown of YAP could down-regulated the expression of PCNA and MMP-2, and inhibit the proliferation and metastasis of gastric cancer cells. In conclusion, YAP is strongly expressed in gastric adenocarcinomas, and knockdown of YAP may inhibit gastric cancer cell proliferation and metastasis through downregulation of PCNA and MMP-2 expression, suggesting that YAP represents an important therapeutic target in human gastric cancer.

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“…YAP is a key effector protein in the Hippo pathway and is negatively regulated by the Mst1/2-LATS1/2-Mob1 complex through direct phosphorylation (11). The phosphorylation of YAP (pYAP) inhibits cell proliferation; therefore, impairment of the Hippo signaling pathway has been implicated in many human cancers including gastric cancer (17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

3,3′-Diindolylmethane suppresses the growth of gastric cancer cells via activation of the Hippo signaling pathway

Park

et al. 2013

Oncology Reports

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Abstract. Recent studies have revealed that 3,3-diindolylmethane (DIM) has antitumor effects in both in vivo and in vitro tumor models. However, the biological function of DIM in human gastric cancer cells is unknown. Genetic and biological studies have confirmed the importance of the novel Hippo tumor-suppressor pathway in regulating cell proliferation, apoptosis, organ size and tumorigenesis in mammals. Thus, the purpose of this study was to investigate the cytotoxic effects of DIM in human gastric cancer cells and to elucidate whether DIM induces cell death by activating the Hippo signaling pathway. Two human gastric cancer cell lines (SNU-1 and SNU-484) were used to investigate the DIM response. DIM significantly inhibited the proliferation of human gastric cancer cells in a dose-dependent manner. The percentage of G1 phase cells increased 24 h following DIM treatment. DIM reduced CDK2, CDK4, CDK6 and cyclin D1 protein levels, while increasing p53 protein levels. DIM induced the levels of cleaved poly(ADP-ribose) polymerase, cleaved-caspase-9, and diminished pro-caspase-3 protein production. In addition, DIM increased pLATS1, Mob1, pMob1, pYAP and Ras association domain family 1 (RASSF1) protein levels and reduced Yap protein production levels. DIM stimulated the binding of RASSF1 with the Mst1/2-LATS1-Mob1 complex, promoting an active Hippo signaling pathway and favoring YAP phosphorylation (pYAP) that inactivates cell proliferation. Furthermore, DIM inhibited the growth of human gastric tumors in a xenograft mouse model. These results indicate that DIM suppresses the growth of gastric cancer cells by activating the Hippo signaling pathway.

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Lentiviral vector-mediated siRNA knockdown of the YAP gene inhibits growth and induces apoptosis in the SGC7901 gastric cancer cell line

Cited by 22 publications

References 28 publications

The retinal determination genedachshundrestricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex

The retinal determination genedachshundrestricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex

Expression and Yes-Associated Protein in Gastric Adenocarcinoma and Inhibitory Effects of its Knockdown on Gastric Cancer Cell Proliferation and Metastasis

3,3′-Diindolylmethane suppresses the growth of gastric cancer cells via activation of the Hippo signaling pathway

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