A Breakdown of the Hippo Pathway in Gastric Cancer

Xu, Zhi Peng; Zhu, Jiangwei; Zhang, Qiang; Wang, Xiaoying

doi:10.5754/hge10669

Cited by 33 publications

(29 citation statements)

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“…LATS family members are core components of the Hippo pathway, which has a key role in intestinal stem cells self-renewal and differentiation [18]. It has been reported that LATS1/2 has decreased expression in the colorectal carcinoma [19] and gastric cancer by promoter hypermethylation [20]. In this study, we found that LATS1/2 was down-regulated in primary appendix and colon carcinomas, which supported the findings as reported.…”

Section: Discussionsupporting

confidence: 93%

Expression of LATS family proteins in ovarian tumors and its significance

Sun

Wang

et al. 2015

Human Pathology

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Section: Discussionsupporting

confidence: 93%

Expression of LATS family proteins in ovarian tumors and its significance

Sun

Wang

et al. 2015

Human Pathology

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“…This cytoplasm-nucleus shifting is involved in cell growth regulation in response to cell-cell contact and cell density. Inactivation of Hippo signaling pathway resulted in nuclear translocation of YAP/TAZ, drove cell proliferation, inhibited cell apoptosis, and eventually led to tumorigenesis (Xu et al, 2011). Some researchers have reported that YAP1 protein increased and localized in nuclear in some human liver and prostate cancers.…”

Section: Discussionmentioning

confidence: 99%

“…In the cytoplasm, YAP/TAZ is phosphorylated and inhibited by a complex, formed by Mst1, LATS1, Mob, WW45, and the phosphorylation results in their association with 14-3-3 protein and cytoplasmic localization (Zhao et al, 2007). In the nucleus, YAP/TAZ bound to the TEAD family transcription factors and then formed a complex, which bound to the specific DNA promoter and initiate gene transcription (Xu et al, 2011). This cytoplasm-nucleus shifting is involved in cell growth regulation in response to cell-cell contact and cell density.…”

Section: Discussionmentioning

confidence: 99%

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Zhou¹,

Li²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1 ,YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for 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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A Breakdown of the Hippo Pathway in Gastric Cancer

Abstract: A breakdown of the Hippo pathway may play a role in tumorigenesis and metastasis of gastric cancer.

Cited by 33 publications

References 0 publications

Expression of LATS family proteins in ovarian tumors and its significance

Expression of LATS family proteins in ovarian tumors and its significance

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

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

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