Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder

Liu, Jian Ye; Li, Yong Hong; Lin, Huan Xin; Liao, Yi; Shi, Juan; Liu, Zhou Wei; Zhang, Zhi Ling; Jiang, Li; Zhang, Jia Xing; Kung, Hsiang Fu; Zeng, Yi Xin; Zhou, Fang; Xie, Dan

doi:10.1186/1471-2407-13-349

Cited by 100 publications

(99 citation statements)

References 29 publications

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“…We observed a decrease of YAP1 and pYAP1 in BCA tissue compared to normal urothelial tissue. During the later courses of our study, Liu et al [18] reported an increase of YAP1 mRNA and protein levels in BCA compared to normal urothelial tissue; furthermore, the expression of YAP1 was predominantly increased in the nucleus. Furthermore, YAP1 expression was correlated with advanced tumor stage and patients survival.…”

Section: Discussionsupporting

confidence: 55%

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer

Latz

Umbach²,

Goltz³

et al. 2015

Urol Int

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Introduction: Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo pathway, plays an important role in many tumor entities. We evaluated staining and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial bladder cancer (BCA). Materials and Methods: We used a tissue micorarray with samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non-muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for comparative analysis. Overall survival and progression-free survival were evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression model. Results: Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in CTRL than in BCA, whereby both - NMIBC and MIBC - had lower levels than CTRL. Among patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate, progression-free, cancer-specific or overall survival. Conclusions: Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is involved in urothelial carcinogenesis.

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Section: Discussionsupporting

confidence: 55%

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer

Latz

Umbach²,

Goltz³

et al. 2015

Urol Int

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“…Tissues and cells were lysed and analyzed by western blotting as described [5] with the following antibodies: rabbit polyclonal anti-YAP1 (1:1,500, ABclonal, MA) and mouse monoclonal anti-β-actin (1:2,000, Sigma). Horseradish peroxidase-conjugated secondary antibodies were acquired from Cell Signaling Technology (1:2,000, CST, MA).…”

Section: Western Blottingmentioning

confidence: 99%

“…Immunohistochemical staining was conducted on formalinfixed paraffin-embedded blocks, as described previously [5].…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

“…YAP1 is a potent oncogene that is up-regulated in diverse cancers [4]. Liu et al [5] observed YAP1 overexpression in bladder cancer tissues, but did not explore its cellular behavior or mechanisms. YAP1 interacts with many proteins to mediate target gene transcription and has been correlated with cell proliferation and tissue expansion through its interactions with, for example, the tumor necrosis factors.…”

Section: Introductionmentioning

confidence: 99%

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The YAP1 oncogene contributes to bladder cancer cell proliferation and migration by regulating the H19 long noncoding RNA

Chen

et al. 2015

Urologic Oncology: Seminars and Original Investigations

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“…High levels of YAP1 protein correlate with cancer progression, and poor prognosis for the bladder, prostate, ovarian and uterine cancer patients [8][9][10][11][12]. In turn, irradiation induced apoptosis of prostate cancer cells has been linked to a decrease in the levels of the YAP1 protein and a consequent raise in the BAX cell death factor [12].…”

Section: Planar Polarity Factors As Potential Tumor Suppressors In Thmentioning

confidence: 99%

Planar Polarity Factors as Potential Tumor Suppressors in the Urogenital Tract

2014

J Androl Gynaecol

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Planar Polarity Factors as Potential Tumor Suppressors in the Urogenital Tractby preventing their nuclear entry and induction of the cyclin E and anti-apoptotic proteins. In the absence of a Hippo signal, YAP and TAZ translocate to the nucleus and form transcriptional complexes with a number of factors, including beta-catenin, to promote cell division, survival, and migratory and invasive cell properties.Loss of FAT function contributes to many types of tumors, including the oral, breast, lung, pancreatic and gastric cancers, melanomas and hepatocellular carcinomas [7]. High levels of YAP1 protein correlate with cancer progression, and poor prognosis for the bladder, prostate, ovarian and uterine cancer patients [8][9][10][11][12]. In turn, irradiation induced apoptosis of prostate cancer cells has been linked to a decrease in the levels of the YAP1 protein and a consequent raise in the BAX cell death factor [12]. Both YAP and TAZ proteins have been implicated in cancer cell migration and metastasis [8,13,14]. The known antagonists of the Hippo pathway include the ciliaassociated protein NPHP4 [15] and the integrin-associated kinase, which mediate inhibition of Lats kinases upstream of the YAP/TAZ phosphorylation. The Lats 1/2 expression levels are downregulated in many advanced and metastatic cancers, including in prostate cancer, and this effect has been linked to cancer cell resistance to the attachment-dependent apoptosis [16].The core PCP pathway can be activated by most Wnt ligands, but has a preference for Wnt5a, Wnt9 and Wnt11, which have been designated as "non-canonical" Wnts. Although the Ft/Ds system is considered as the long distance PCP component, the core PCP pathway also has long distance capabilities, enabled by the diffusion of the Wnt ligands [17]. Formation of the Wnt/Fzd complexes is the first step in both the core PCP and Wnt/beta-catenin pathways. Thus, the former is often referred to as the "non-canonical Wnt" signaling. Assembly of the Fzd and Vangl receptor complexes on the apical cell surface appears to favor the PCP pathway [18]. In contrast to the canonical Wnt signaling, the core PCP pathway does not affect nuclear localization of beta-catenin. Furthermore, the core PCP signaling routinely antagonizes the canonical Wnt pathway, first, by recruiting Dvl to the membrane Vangl2 complexes, and also by sequestering other shared components (Wnts, Fzd and Frodo) and promoting the degradation of beta-catenin [19]. The canonical Wnt/beta-catenin signaling is often upregulated in cancers. Therefore, part of the PCP tumor suppressor role is likely exercised simply by suppressing the canonical Wnt targets, while another part is associated with its role in the maintenance of tissue polarity and cohesion.

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Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder

Cited by 100 publications

References 29 publications

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer

The YAP1 oncogene contributes to bladder cancer cell proliferation and migration by regulating the H19 long noncoding RNA

Planar Polarity Factors as Potential Tumor Suppressors in the Urogenital Tract

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