Reciprocal Crosstalk Between YAP1/Hippo Pathway and the p53 Family Proteins: Mechanisms and Outcomes in Cancer

Raj, Nitin; Bam, Rakesh

doi:10.3389/fcell.2019.00159

Cited by 74 publications

(67 citation statements)

References 99 publications

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“…Contrarily, it has been reported that tumor suppressors, including RASSF1A and p53, negatively regulate YAP by activating the Hippo kinase cascade. The loss of function mutations of RASSF1A or p53, contributes to increased YAP expression in cancers [ 74 , 117 ].…”

Section: Hippo/yap Singing Pathway In Nsclcmentioning

confidence: 99%

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Hsu

Yang

Jablons

et al. 2020

Cancers

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The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src–YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted.

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Section: Hippo/yap Singing Pathway In Nsclcmentioning

confidence: 99%

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Hsu

Yang

Jablons

et al. 2020

Cancers

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“…The activation of the Hippo signaling pathway is characterized by the upstream kinase-induced phosphorylation of its downstream effectors, including YAP1, resulting in the nuclear exclusion of YAP1, and ultimately, its cytoplasmic degradation. 26,27 Taken together, the aforementioned findings indicated that circTADA2A could downregulate miR-129-5p, thereby enhancing YAP1 and TRPS1 expression. However, miR-129-5p downregulation prevented the phosphorylation of YAP1 and its cytoplasmic degradation, thus contributing to OS cell proliferation and drug resistance.…”

mentioning

confidence: 74%

<p>TRPS1 and YAP1 Regulate Cell Proliferation and Drug Resistance of Osteosarcoma via Competitively Binding to the Target of circTADA2A – miR-129-5p</p>

Zhang¹,

Ji²,

Zhou³

et al. 2020

OTT

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Introduction: The yes-associated protein (YAP) and trichorhinophalangeal syndrome 1 (TRPS1) have been reported to account for the pathogenesis of cancers and may play an important role in osteosarcoma (OS). This study intended to investigate the modulatory effect and relationship of TRPS1 and YAP1 in OS cells. Methods: The expression difference of YAP1 and TRPS1 in OS cells was measured. Then, the effect of circTADA2A silence on YAP1 and TRPS1 expression as well as OS proliferation and drug resistance was estimated. Results: TRPS1 and YAP1 were upregulated in OS cell lines, and TRPS1 and YAP1 were highly expressed in MG63 and U2OS cells, respectively. The cell proliferation of MG63 was lower than that of U2OS, but the opposite result was observed in the presence of cisplatin (DDP). CircTADA2A was upregulated while miR-129-5p was downregulated in MG63 and U2OS cells compared. Besides, circTADA2A knockdown inhibited cell proliferation and reduced DDP resistance in both MG63 and U2OS. MiR-129-5p was increased but TRPS1 and YAP1 were decreased by circTADA2A knockdown. Meanwhile, circTADA2A knockdown reduced TRPS1 protein expression but enhanced phosphorylated (p)-YAP1. In xenograft OS tumor mice, circTADA2A knockdown inhibited tumor growth in the absence or presence of DDP. Finally, miR-129-5p could bind to circTADA2A, TRPS1 and YAPS. Discussion: CircRNA TADA2A could target miR-129-5p, which was competitively bound by TRPS1 and YAP1, thereby regulating OS cell proliferation and drug resistance.

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“…Recent researches have pointed to an important role for YAP1 signaling in tumor progression [30]. As the wellcharacterized downstream transcriptional coactivator of the Hippo pathway, YAP1 has been demonstrated to be highly activated in many tumors.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0085576 promotes clear cell renal cell carcinoma tumorigenesis and metastasis through the miR-498/YAP1 axis

Liu

Zhou

Piao

et al. 2020

Aging

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There is emerging evidence that circular RNAs (circRNAs) act as important regulators in various cancers. It is less clear, however, what role circRNA plays in the tumorigenesis and metastasis of clear cell renal cell carcinoma (ccRCC). In this study, using bioinformatics analysis and a series of experimental analysis, we characterized a novel circRNA, hsa_circ_0085576 was up-regulated in ccRCC tissues and cell lines. High hsa_circ_0085576 expression was significantly correlated with tumor size, clinical stage, and metastasis status and poorer survival. Knockdown of hsa_circ_0085576 notably inhibited cell proliferation, migration, invasion, whereas enhanced cell apoptosis of ccRCC cells, in vitro. In contrast, overexpression of hsa_circ_0085576 had the opposite effects. Moreover, hsa_circ_0085576 silencing significantly suppressed tumor growth and metastasis, whereas overexpression of hsa_circ_0085576 had the opposite effects, in vivo, Our results further showed that hsa_circ_0085576 acted as a competitive endogenous RNAs to interact with microRNA-498, to attenuate its repressive effect on target gene Yes-associated protein 1 (YAP1). Finally, functional studies revealed that inhibition of hsa_circ_0085576 suppressed cell growth and metastasis by regulating miR-498/YAP1 signaling, in ccRCC cells. Based on these findings, hsa_circ_0085576 may represent a valuable prognostic biomarker and a potential therapeutic target to curb the tumorigenesis and metastasis of ccRCC.

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Reciprocal Crosstalk Between YAP1/Hippo Pathway and the p53 Family Proteins: Mechanisms and Outcomes in Cancer

Cited by 74 publications

References 99 publications

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

<p>TRPS1 and YAP1 Regulate Cell Proliferation and Drug Resistance of Osteosarcoma via Competitively Binding to the Target of circTADA2A – miR-129-5p</p>

Hsa_circ_0085576 promotes clear cell renal cell carcinoma tumorigenesis and metastasis through the miR-498/YAP1 axis

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