YAP Expression and Activity Are Suppressed by S100A7 via p65/NFκB-mediated Repression of ΔNp63

Li, Yunguang; Kong, Fei; Shao, Qirui; Wang, Rui; Hu, Enze; Jin, Ling; Chang, Jin; He, Dacheng; Xiao, Xueyuan

doi:10.1158/1541-7786.mcr-17-0349

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…A previous study demonstrated that S100A7 repressed the expression of YAP and inhibited the expression of ΔNp63, which directly binds to the region of the YAP promoter and induces its expression, inhibiting the Hippo pathway and enhancing YAP activity. S100A7 also enhances the resistance of squamous cell carcinoma cancer cells by inhibiting the expression and activity of YAP ( 34 ). Taken together, the findings of the present study demonstrate that S100A1 regulated the aggressiveness of HCC mainly through the YAP and Hippo signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma

et al. 2018

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Despite advances in surgery and chemotherapy, the prognosis of patients with hepatocellular carcinoma (HCC) remains poor. In the present study, the role of S100A1 in the progression of HCC was investigated. Immunohistochemical staining was used to measure the expression of S100A1 in HCC tissues. S100A1 was knocked down by siRNA. A battery of experiments was used to evaluate the biology functions of S100A1. It was found that S100A1 was upregulated in HCC tissues, and its upregulation was associated with a large tumor size, low differentiation and shorter survival time. The biological experiments demonstrated that S100A1 functions as an oncogene in HCC. It was also found that S100A1 knockdown enhanced the inhibitory effects of cisplatin on HCC cells. The results showed that the downregulation of S100A1 induced the phosphorylation of yes-associated protein (YAP), and treatment with CHX demonstrated that the downregulation of S100A1 accelerated YAP protein degradation. The downregu-lation of S100A1 did not alter the expression of mammalian sterile 20-like kinase (MST)1/2 or phosphorylated MST1/2, but upregulated the phosphorylation of large tumor suppressor kinase 1 (LATS1). It was further confirmed that S100A1 interacted with LATS1. LATS1 depletion significantly reduced the effects of S100A1 on cell growth rate and apoptosis, and there was a positive correlation between phosphorylated LATS1 and S100A1 in clinical samples, indicating that LATS1 was responsible for the S100A1-induced changes in cancer cell growth and Hippo signaling. In conclusion, the results of the present study indicated that S100A1 functions as an oncogene and may be a biomarker for the prognosis of patients with HCC. S100A1 exerted its oncogenic function by interacting with LATS1 and activating YAP. S100A1 may serve as a target for novel therapies in HCC.

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Section: Discussionmentioning

confidence: 99%

Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma

et al. 2018

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“…Both YAP immunolabeling scores and percentage of ΔNp63- positive cells in all samples were high in OSCC. In previous study, ΔNp63 was shown to not only directly bind to the region of YAP promoter and induce its expression but also enhance YAP activity in SCC cell lines14. However, Ehsanian R et al show that ΔNp63 inhibits YAP expression, binds the YAP promoter, and suppresses cell death in SCC cell lines19.…”

Section: Discussionmentioning

confidence: 95%

“…Furthermore, elevated expression of ΔNp63 in esophageal squamous cell carcinoma and laryngeal squamous cell carcinoma was reported. Recently, ΔNp63 was shown to not only directly bind to the region of YAP promoter and induce its expression but also enhance YAP activity in squamous cell carcinoma 14. However, there are few studies that described the relationship between YAP and ΔNp63 in carcinogenesis and progression of OSCC of human tissue specimens.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemistry of YAP and dNp63 and survival analysis of patients bearing precancerous lesion and oral squamous cell carcinoma

Ono¹,

Nakano²,

Takabatake³

et al. 2019

Int. J. Med. Sci.

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Background: Yes-associated protein (YAP) is a candidate oncogene in various human cancers, and recently, it has been reported that YAP expression and its activity was enhanced by ΔNp63. However, the role of YAP and ΔNp63 expression in carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has been unknown. Therefore, we investigated how YAP and ΔNp63 influence carcinogenesis and progression of OSCC. Methods: We performed immunohistochemical analyses in whole tissue samples to investigate YAP and ΔNp63 expression in normal oral mucosa, epithelial hyperplasia, oral epithelial dysplasia (OED; low/high grade), carcinoma in situ (CIS), and OSCC. Furthermore, in OSCC, we analyzed clinical significance by using Kaplan-Meier survival analysis. Results: In normal oral mucosa and epithelial hyperplasia, YAP expression was primarily confined to the basal and parabasal layers, but YAP expression was elevated in OED, CIS, and OSCC. In OED, YAP and ΔNp63 expression levels were markedly higher in high grade than in low grade. In OSCC groups, YAP and ΔNp63 expression patterns tended to differ according to histopathological differentiation of OSCC. Furthermore, the YAP high expression group, which showed YAP staining in >50% positive cells with strong cytoplasmic staining or >10% positive cells with nuclear reactivity, showed a tendency to have a poor survival rate. Conclusion: YAP and ΔNp63 expression levels correlated with grade of oral OED. Additionally, YAP expression was associated with OSCC survival rate. Our results suggested that YAP and ΔNp63 expression might serve as predictive markers to distinguish OSCC development and progression.

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“…Interestingly, Ehsanian et al observed that deltaNp63 binds to the promotor of YAP and suppresses YAP expression in head and neck cancer cells [111]. Surprisingly, Li et al also observed that deltaNp63 directly binds to the YAP promoter, but claimed that this induces YAP gene expression in squamous cell carcinoma cell lines [112]. Possibly, the effect of deltaNp63 on gene expression of target genes depends on many additional transcription factors, which might be differently expressed in distinct cell lines.…”

Section: A Multitude Of Molecules Regulate Apoptosis and Hippo-yapmentioning

confidence: 99%

The Ambivalent Function of YAP in Apoptosis and Cancer

Zhang

Abdelrahman

Vollmar

et al. 2018

IJMS

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Yes-associated protein, a core regulator of the Hippo-YAP signaling pathway, plays a vital role in inhibiting apoptosis. Thus, several studies and reviews suggest that yes-associated protein is a good target for treating cancer. Unfortunately, more and more evidence demonstrates that this protein is also an essential contributor of p73-mediated apoptosis. This questions the concept that yes-associated protein is always a good target for developing novel anti-cancer drugs. Thus, the aim of this review was to evaluate the clinical relevance of yes-associated protein for cancer pathophysiology. This review also summarized the molecules, processes and drugs, which regulate Hippo-YAP signaling and discusses their effect on apoptosis. In addition, issues are defined, which should be addressed in the future in order to provide a solid basis for targeting the Hippo-YAP signaling pathway in clinical trials.

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YAP Expression and Activity Are Suppressed by S100A7 via p65/NFκB-mediated Repression of ΔNp63

Cited by 11 publications

References 48 publications

Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma

Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma

Immunohistochemistry of YAP and dNp63 and survival analysis of patients bearing precancerous lesion and oral squamous cell carcinoma

The Ambivalent Function of YAP in Apoptosis and Cancer

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