YAP regulates cell proliferation, migration, and steroidogenesis in adult granulosa cell tumors

Fu, David; Lv, Xiaozhen; Hua, Guohua; He, Chunbo; Dong, Jixin; Lele, Subodh M.; Li, David Wan Cheng; Zhai, Qiong-Li; Davis, John S.; Wang, Cheng

doi:10.1530/erc-13-0339

Cited by 84 publications

(100 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with reports in other cell lines (10,41), ablation of YAP in LPCs decreased cellular proliferation (Fig. 1A) in cells with undetectable YAP expression as determined by Western blot (Fig.…”

Section: Resultssupporting

confidence: 91%

TAZ Protein Accumulation Is Negatively Regulated by YAP Abundance in Mammalian Cells

Finch-Edmondson

Strauss

Passman

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Hippo pathway effectors YAP and TAZ are transcriptional coactivators that regulate cellular proliferation and tumorigenesis. Results: YAP negatively regulates TAZ abundance in a GSK-3-dependent manner. Conclusion: Changes in YAP abundance results in compensatory changes in TAZ to maintain Hippo signaling homeostasis. Significance: This initial reporting of a direct relationship between YAP and TAZ abundances has profound implications for understanding their biological functions.

show abstract

Section: Resultssupporting

confidence: 91%

TAZ Protein Accumulation Is Negatively Regulated by YAP Abundance in Mammalian Cells

Finch-Edmondson

Strauss

Passman

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Moreover, the change in pYAP1 expression is similar to that of YAP1, but the ratio of pYAP1/YAP1 decreased significantly among 7D, 2M and 20M mice. High cell-density activates the Hippo pathway kinases and promotes the phosphorylation of YAP1 on serine 127, which leads to its nuclear export and growth inhibition [47,48]. Furthermore, the results show that Hippo signaling genes are active in different stages of mouse ovarian cortex, and OGSCs had a positive correlation with the level of MST1 and LATS2 and were contrary to the changes in YAP1 expression.…”

Section: Discussionmentioning

confidence: 99%

Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

Zhou

Zheng

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether the Hippo signaling pathway plays a role in the development of Ovarian Germline Stem Cells (OGSCs) during physiological and pathological ovarian aging in mice is unknown. Methods: Mice at the age of 7 days (7D), or of 2, 10, or 20 months (2M, 10M, 20M) and mice at 2M treated with TPT and CY/BUS drugs were selected as physiological and pathological ovarian aging models, respectively. Immunohistochemistry was used to assess the development of follicles, and the co-localization of genes characteristic of OGSCs with MST1, LATS2 and YAP1 was assessed by immunofluorescence, western blotting and real-time PCR methods. Results: The Hippo signal pathway and MVH/OCT4 genes were co-expressed in the mouse ovarian cortex. The level and co-localization of LATS2, MST1, MVH, and OCT4 were significantly decreased with increased age, but YAP1 was more prevalent in the mouse ovarian cortex of 2M mice than 7D mice and was not observed in 20M mice. Furthermore, YAP1, MVH, and OCT4 were gradually decreased after TPT and CY/BUS treatment, and LATS2 mRNA and protein up-regulation persisted in TPT- and CY/BUS-treated mice. However, the expression of MST1 was lower in the TPT and CY/BUS groups compared with the control group. In addition, pYAP1 protein showed the highest expression in the ovarian cortexes of 7D mice compared with 20M mice, and the value of pYAP1/YAP1 decreased from 7D to 20M. Moreover, pYAP1 decreased in the TPT- and CY/BUS-treated groups, but the value of pYAP1/YAP1 increased in these groups. Conclusion: Taken together, our results show that the Hippo signaling pathway is associated with the changes that take place in OGSCs during physiological and pathological ovarian aging in mice. Thus, the Hippo signaling pathway may be involved in the development schedule of OGSCs.

show abstract

“…During Drosophila oogenesis, Hippo signaling activity is required for oocyte polarization and regulation of somatic follicle-cell proliferation and differentiation in Drosophila follicle cells [14,15]. In mammals, overexpression of YAP enhances tumor formation and growth, whereas down-regulation of YAP decreases the tumor formation and growth in kinds of cancer cell lines [16]. The transcriptional co-activator with PDZ-binding motif (TAZ) is a transcriptional effector of the Hippo signaling cascade in regulating cell proliferation tumorigenesis [13,17].…”

Section: Introductionmentioning

confidence: 99%

Hippo Signaling Pathway Reveals a Spatio-Temporal Correlation with the Size of Primordial Follicle Pool in Mice

Xiang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: The Hippo signaling pathway, a highly conserved cell signaling system, exists in most multicellular organisms and regulates cell proliferation, differentiation, and apoptosis. It has been reported that the members of Hippo signaling are expressed in mammalian ovaries, but the exact functions of this pathway in primordial follicle development remains unclear. Methods: To analyze the spatio-temporal correlation between the core component of Hippo pathway and the size of primordial follicle pool, Western blot, Real-time PCR and immunohistochemistry were used, and the expression and localization of MST1, LATS2 and YAP1 mRNA and protein were examined in 3 d, 1 m, 5 m, 16 m postnatal mice ovary and the culture model of mice primordial follicle in vitro. Results: Both the protein and mRNA expression of the MST1 and LATS2 were decreased significantly as mouse age increased (p < 0.05), however, the mRNA expression of them increased significantly in 16 m compared with 5 m as well as the protein expression of LATS2.The expression of YAP showed the opposite trend, and the significant protein expression of pYAP was increased before 1 m, after which no significant change was observed. Moreover, the ratio of pYAP/YAP decreased significantly. Culturing ovaries for 8 d in vitro resulted in the activation of primordial follicles in 3 d postnatal mice ovaries, and these developed into primary follicles with the expression of PCNA increasing significantly (p < 0.05). The mRNA and protein expression of MST and LATS decreased significantly (p < 0.05), and the expression of YAP increased significantly (p < 0.05, p < 0.01), whereas the ratio of pYAP/YAP decreased significantly (p < 0.05). Conclusion: The above results reveal that the expression of the core components of Hippo pathway changed during mouse follicular development, especially before and after primordial follicle activation in vitro. The primordial follicle activation may be related to the significant decrease of the ratio of pYAP1/YAP1. In conclusion, Hippo signaling pathway expressed in mice ovaries and have spatio-temporal correlation with the size of primordial follicle pool.

show abstract

YAP regulates cell proliferation, migration, and steroidogenesis in adult granulosa cell tumors

Cited by 84 publications

References 63 publications

TAZ Protein Accumulation Is Negatively Regulated by YAP Abundance in Mammalian Cells

TAZ Protein Accumulation Is Negatively Regulated by YAP Abundance in Mammalian Cells

Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

Hippo Signaling Pathway Reveals a Spatio-Temporal Correlation with the Size of Primordial Follicle Pool in Mice

Contact Info

Product

Resources

About