The Hippo Signaling Pathway Components Lats and Yap Pattern Tead4 Activity to Distinguish Mouse Trophectoderm from Inner Cell Mass

Nishioka, Noriyuki; Inoue, Ken; Adachi, Kenjiro; Kanazawa, Hiroshi; Ota, Masahiro; Ralston, Amy; Yabuta, Norikazu; Hirahara, Shino; Stephenson, Robert O.; Ogonuki, Narumi; Makita, Ryosuke; Kurihara, Hiroki; Morin‐Kensicki, Elizabeth; Nishimura, Hiroshi; Rossant, Janet; Nakao, Kazuki; Niwa, Hitoshi; Sasaki, Hiroshi

doi:10.1016/j.devcel.2009.02.003

Cited by 886 publications

(1,071 citation statements)

References 56 publications

(109 reference statements)

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“…These findings suggest that Oct4 may suppress the activation of cancer cells. In Noriyuki Nishioka,s research (Nishioka et al, 2009), they have proposed that CDX2 is the major target of TEAD4, and Tead4 is dispensable for CDX2 expression when Oct3/4 levels are reduced, suggesting that Tead4 can induce cdx2 expression by overcoming Oct4 mediated suppression. Our study discovered that the expression of CDX2 had a positive correlation with TEAD1, and a negative correlation with OCT4, which were consistent with the results of Noriyuki Nishioka's research.…”

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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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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“…Recent genetic studies found the Hippo pathway transcription factor TEAD4 as a determinant of TE specification (Yagi et al, 2007;Nishioka et al, 2008). Further studies suggest a model that the Hippo pathway was inactivated in outer cells during blastocyst formation due to cell "crowdness," which activates YAP to drive TEAD4-dependent expression of TE-specific genes such as Cdx2 (Nishioka et al, 2009). In ICM, the Hippo pathway remains active and YAP is inhibited to prevent TE-specific gene expression.…”

Section: The Hippo Pathway Regulates Es Cell Self-renewal and Ips Celmentioning

confidence: 99%

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

et al. 2012

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This pathway was first found to inhibit cell proliferation and promote apoptosis, therefore regulating cell number and organ size in both Drosophila and mammals. However, in several organs, disturbance of the pathway leads to specific expansion of the progenitor cell compartment and manipulation of the pathway in embryonic stem cells strongly affects their self-renewal and differentiation. In this review, we summarize current observations on roles of the Hippo pathway in different types of stem cells and discuss how these findings changed our view on the Hippo pathway in organ development and tumorigenesis.

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“…This regulatory interaction allows the embryo to shift from the impasse where the Oct3/4 network maintains the future embryonic cells in an undifferentiated pluripotent state preventing gastrulation and differentiation. In trophectoderm differentiation, the Hippo signaling pathway regulates the allocation of the Cdx2 expressing trophoblast cells and the inner cell mass cells expressing Oct3/4, suggesting a different mode of regulation (Nishioka et al, 2009). During gastrulation, the prospective germ layer cells themselves have to undergo differentiation requiring the repression of Oct3/4 expression and other genes functioning with it, thus marking the end of pluripotency.…”

Section: Cross-regulation Betweenmentioning

confidence: 99%

Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation

et al. 2011

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Gastrulation marks the onset of germ layer formation from undifferentiated precursor cells maintained by a network including the Pou5f1 gene, Oct3/4. Negative regulation of the undifferentiated state is a prerequisite for germ layer formation and subsequent development. A novel cross-regulatory network was characterized including the Pou5f1 and Cdx1 genes as part of the signals controlling the onset of gastrulation. Of particular interest was the observation that, preceding gastrulation, the Xenopus Oct3/4 factors, Oct60, Oct25, and Oct91, positively regulate Cdx1 expression through FGF signaling, and during gastrulation the Oct3/4 factors become repressors of Cdx1. Cdx1 negatively regulates the Pou5f1 genes during gastrulation, thus contributing to the repression of the network maintaining the undifferentiated state and promoting the onset of gastrulation. These regulatory interactions suggest that Oct3/4 initiates its own negative autoregulation through Cdx1 up-regulation to begin the repression of pluripotency in preparation for the onset of gastrulation and germ layer differentiation. Developmental Dynamics 240:796-807,

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The Hippo Signaling Pathway Components Lats and Yap Pattern Tead4 Activity to Distinguish Mouse Trophectoderm from Inner Cell Mass

Cited by 886 publications

References 56 publications

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation

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