Roles of RUNX in Hippo Pathway Signaling

Passaniti, Antonino; Brusgard, Jessica L.; Qiao, Yiting; Sudol, Marius; Finch-Edmondson, Megan

doi:10.1007/978-981-10-3233-2_26

Cited by 34 publications

(27 citation statements)

References 97 publications

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“…The core Hippo pathway consists of a kinase cascade: the upstream kinase MST1/2 phosphorylates and activates the downstream kinase LATS1/2, leading to phosphorylation and inactivation of the transcriptional coactivator Yes-associated protein (YAP1) ( 4 – 6 ). Then, the phosphorylated YAP1 translocates to the nucleus and associates with transcription factors, such as the TEA domain (TEAD) family, RUNX, and SMADs ( 7 – 9 ), consequently favoring an accelerated rate of cell growth, invasiveness, and survival. Upregulation of YAP1 expression and its nuclear translocation are frequently detected in several human cancers, including breast cancer, hepatocellular carcinoma, and GC ( 10 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein

et al. 2021

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The Yes-associated protein (YAP1) is a main effector of the canonical Hippo pathway, which contributes greatly to tumor initiation, progression, and metastasis in multiple cancers, including gastric cancer (GC). Due to limited knowledge of YAP1 upregulation in cancer, it is a great challenge of therapeutic targets toward the Hippo–YAP1 pathway. Here, we identify nucleolar spindle-associated protein 1 (NUSAP1) as a novel binding partner of YAP1. The upregulation of NUSAP1 is associated with unfavorable clinical outcomes in GC patients, and NUSAP1 depletion impairs its oncogenic properties in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 functions as a positive regulator of YAP1 protein stability, thereby inducing the transcription of Hippo pathway downstream target genes, such as CTGF and CYR61. More interestingly, we find that the cancer-promoting effects of NUSAP1 on GC cell growth, migration, and invasion are mainly mediated by YAP1. Furthermore, aberrant expression of NUSAP1 and YAP1 is highly correlated in GC cell lines and tissues. We herein clarify the role of the oncogenic NUSAP1–YAP1 axis in GC tumorigenesis and progression and, therefore, provide novel therapeutic targets for GC treatment.

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Section: Introductionmentioning

confidence: 99%

NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein

et al. 2021

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“…13,20 Besides, YAP/TAZ could trans-activate many transcriptional factors, including RUNX, TEAD and AP1 family members. 10,21,22 YAP mediated quite a few cancer phenotypes, such as migration, invasion, 'stemness' and EMT (epithelial-mesenchymal transition) in human cancers. In oesophageal cancer, the dysregulation of Hippo signalling, such as YAP gene amplification and FAT mutations were found in 40% of all oesophageal cancer samples.…”

Section: Discussionmentioning

confidence: 99%

“…For example, YAP gene amplification was found in liver cancer, triple‐negative breast cancer and ESCC 13,20 . Besides, YAP/TAZ could trans‐activate many transcriptional factors, including RUNX, TEAD and AP1 family members 10,21,22 . YAP mediated quite a few cancer phenotypes, such as migration, invasion, ‘stemness’ and EMT (epithelial‐mesenchymal transition) in human cancers.…”

Section: Discussionmentioning

confidence: 99%

RACO‐1 modulates Hippo signalling in oesophageal squamous cell carcinoma

Pang

Wang

Zhou

et al. 2020

J Cellular Molecular Medi

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“…The core Hippo pathway consists of a kinase cascade: the upstream kinase MST1/2 phosphorylates and activates the downstream kinase LATS1/2, leading to phosphorylation and inactivation of the transcriptional coactivator YAP [4][5][6]. Then the phosphorylated YAP translocates to the nucleus and associates with transcription factors, such as the TEA domain (TEAD) family, RUNX and SMADs [7][8][9], consequently favoring an accelerated rate of cell growth, invasiveness and survival. Upregulation of YAP expression and its nuclear translocation have been frequently detected in several human cancers, including breast cancer, hepatocellular carcinoma and GC [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

Guo¹,

Zou²,

Zhou³

et al. 2020

Preprint

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Background:Nucleolar and spindle associated protein (NUSAP1) is involved in tumor initiation, progression and metastasis. However, there are limited studies regarding the role of NUSAP1 in gastric cancer (GC). Methods: The expression profile and clinical significance of NUSAP1 in GC were analysed in online database using GEPIA, Oncomine and KM plotter, which was further confirmed in clinical specimens.The functional role of NUSAP1 were detected utilizing in vitro and in vivo assays. Western blotting, qRT-PCR, the cycloheximide-chase, immunofluorescence staining and Co-immunoprecipitaion (Co-IP) assays were performed to explore the possible molecular mechanism by which NUSAP1 stabilizes YAP protein. Results:In this study, we found that the expression of NUSAP1 was upregulated in GC tissues and correlates closely with progression and prognosis. Additionally, abnormal NUSAP1 expression promoted malignant behaviors of GC cells in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 physically interacts with YAP and furthermore stabilizes YAP protein expression, which induces the transcription of Hippo pathway downstream target genes. Furthermore, the effects of NUSAP1 on GC cell growth, migration and invasion were mainly mediated by YAP. Conclusions:Our data demonstrates that the novel NUSAP1-YAP axis exerts an critical role in GC tumorigenesis and progression, and therefore could provide a novel therapeutic target for GC treatment.

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Roles of RUNX in Hippo Pathway Signaling

Cited by 34 publications

References 97 publications

NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein

NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein

RACO‐1 modulates Hippo signalling in oesophageal squamous cell carcinoma

NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

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