Targeting YAP and Hippo signaling pathway in liver cancer

Liu, Angela M.; Xu, Zhi; Chen, Jinfei; Poon, Ronnie Tung‐Ping; Luk, John M.

doi:10.1517/14728222.2010.499361

Cited by 89 publications

(65 citation statements)

References 141 publications

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“…Overexpression of YAP1 leads to loss of contact inhibition and increases the organ size (Huang et al 2005;Camargo et al 2007). Dysregulation of YAP1 has been identified in various types of cancer (Yuan et al 2008;Liu et al 2010;Wu et al 2010;Orr et al 2011;Zhang et al 2011;Diep et al 2012). Because of its crucial function in tissue growth and tumor development, YAP1 and its regulation have been studied extensively.…”

Section: Discussionmentioning

confidence: 99%

PTPN14 is required for the density-dependent control of YAP1

et al. 2012

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Through an shRNA-mediated loss-of-function screen, we identified PTPN14 as a potential tumor suppressor. PTPN14 interacts with yes-associated protein 1 (YAP1), a member of the hippo signaling pathway. We showed that PTPN14 promotes the nucleus-to-cytoplasm translocation of YAP1 during contact inhibition and thus inhibits YAP1 transactivation activity. Interestingly, PTPN14 protein stability was positively controlled by cell density. We identified the CRL2 LRR1 (cullin2 RING ubiquitin ligase complex/leucine-rich repeat protein 1) complex as the E3 ligase that targets PTPN14 for degradation at low cell density. Collectively, these data suggest that PTPN14 acts to suppress cell proliferation by promoting cell density-dependent cytoplasmic translocation of YAP1.

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Section: Discussionmentioning

confidence: 99%

PTPN14 is required for the density-dependent control of YAP1

et al. 2012

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“…Thus, using shRNA to knockdown YAP may produce tumor-suppressing effects. RNAimediated knockdown of YAP in HCC cells leads to decreased cell proliferation and adhesion (21). YAP gene targeting by RNAi can inhibit the migration, invasion, anchorage-independent growth and angiogenesis of gastric cells (22).…”

Section: Effect Of Knockdown Of Yap On Gastric Cancer Cell Metastasismentioning

confidence: 99%

Expression and Yes-Associated Protein in Gastric Adenocarcinoma and Inhibitory Effects of its Knockdown on Gastric Cancer Cell Proliferation and Metastasis

Zhang

Yang

et al. 2012

Int J Immunopathol Pharmacol

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Yes-associated protein (YAP) has been implicated as an oncogene in multiple human cancers. In the present study, human gastric adenocarcinoma tissues of different grades (N=78) were collected and the mRNA and protein expression of YAP and phosphorylated YAP (p-YAP) in gastric adenocarcinomas were evaluated using immunohistochemistry, Real-time PCR and Western blot assays. Then, human gastric cancer SGC-7901 cells were stably transfected with lentivirus-mediated YAP small hairpin RNA (shRNA). The expression levels ofYAP,proliferating cell nuclear antigen (PCNA) and metalloproteinase-2 (MMP-2) were detected and the effects of shRNA-mediated knockdown ofYAP on cell proliferation and metastasis were assessed in gastric cancer cells. As a result, the expression ofYAP was observed in 69.23% gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Knockdown of YAP could down-regulated the expression of PCNA and MMP-2, and inhibit the proliferation and metastasis of gastric cancer cells. In conclusion, YAP is strongly expressed in gastric adenocarcinomas, and knockdown of YAP may inhibit gastric cancer cell proliferation and metastasis through downregulation of PCNA and MMP-2 expression, suggesting that YAP represents an important therapeutic target in human gastric cancer.

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“…The signalling cascade of this pathway ultimately leads to the phosphorylation of yes-associated protein (YAP), a downstream effector of this pathway. YAP is a transcriptional co-activator and its phosphorylation causes it to remain in the cytoplasm and prevent the transcription of genes responsible for cell proliferation and inhibition of apoptosis [105] . Recently, a few studies have described the Hippo pathway as a negative regulator of Wnt/β-catenin signalling [106,107] .…”

Section: Yes-associated Proteinmentioning

confidence: 99%

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Fatima¹

2011

WJCO

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Liver cancer is the fifth and seventh most common cause of cancer in men and women, respectively. Wnt/β-catenin signalling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma (HCC). Based on the current understanding, this article summarizes the possible mechanisms for the aberrant activation of this pathway with specific focus on HCC. Furthermore, we will discuss the role of dickkopfs (DKKs) in regulating Wnt/β-catenin signalling, which is poorly understood and understudied. DKKs are a family of secreted proteins that comprise at least four members, namely DKK1-DKK4, which act as inhibitors of Wnt/β-catenin signalling. Nevertheless, not all members antagonize Wnt/β-catenin signalling. Their functional significance in hepatocarcinogenesis remains to be further characterized for which these studies should provide new insights into the regulatory role of DKKs in Wnt/β-catenin signalling in hepatic carcinogenesis. Because of the important oncogenic roles, there are an increasing number of therapeutic molecules targeting β-catenin and the Wnt/ β-catenin pathway for potential therapy of HCC. hepatocellular carcinoma anD the unmet meDical neeDSLiver cancer ranks the fifth most common cancer in men and the second leading cause of cancer-related death. In women, it is the seventh most frequent cancer and sixth leading cause of cancer death [1] . Hepatocellular carcinoma (HCC) is the most common primary malignancy of liver. Men are three times more likely to develop HCC than women and the incidence increases with age [2] . HCC is prevalent in Asia and Africa, but recently it is on the rise in the Western world due to an increase in hepatitis C virus (HCV) infection [3] . Risk factors for HCC include chronic hepatitis B virus (HBV) and HCV infections, cirrhosis, chronic alcohol abuse, aflatoxin ingestion, non-alcoholic steatohepatitis and other metabolic liver diseases [4,5] . Much of HCC occurs in the background of cirrhosis. About 80%-90% of patients with cirrhosis go on to develop HCC eventually and the remaining 10%-20% of cases develop HCC without cirrhosis. Furthermore, HBV and HCV infections increase the risk of developing cirrhosis and later HCC. Among the HCC

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Targeting YAP and Hippo signaling pathway in liver cancer

Abstract: YAP is a key oncogenic driver in liver carcinogenesis and deregulation of the Hippo pathway causes tumor formation and malignancy. Targeting YAP and cognate downstream signaling targets may have clinical utility in cancer therapies.

Cited by 89 publications

References 141 publications

PTPN14 is required for the density-dependent control of YAP1

PTPN14 is required for the density-dependent control of YAP1

Expression and Yes-Associated Protein in Gastric Adenocarcinoma and Inhibitory Effects of its Knockdown on Gastric Cancer Cell Proliferation and Metastasis

Dickkopfs and Wnt/β-catenin signalling in liver cancer

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