The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer

Cunningham, Richard; Hansen, Carsten Gram

doi:10.1042/cs20201474

Cited by 105 publications

(91 citation statements)

References 320 publications

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“…Disruption of the Hippo pathway is observed in multiple cancer types and occurs both at the genomic and post-translational levels. Potentially owing to its important role in early embryogenesis, inactivating mutations of individual components within the kinase cascade are rare and mainly somatic [ 40 , 41 , 42 ]. Briefly, upon activation of the Hippo pathway, STK4/3 (MST1/2) kinases phosphorylate LATS1/2 kinases along with the adaptor protein MOB1, in response to various stimuli.…”

Section: The Hippo Pathway In Prostate Cancermentioning

confidence: 99%

Interplay of Developmental Hippo–Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer

Mourkioti

Angelopoulou

Belogiannis

et al. 2022

Cells

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Prostate cancer belongs in the class of hormone-dependent cancers, representing a major cause of cancer incidence in men worldwide. Since upon disease onset almost all prostate cancers are androgen-dependent and require active androgen receptor (AR) signaling for their survival, the primary treatment approach has for decades relied on inhibition of the AR pathway via androgen deprivation therapy (ADT). However, following this line of treatment, cancer cell pools often become resistant to therapy, contributing to disease progression towards the significantly more aggressive castration-resistant prostate cancer (CRPC) form, characterized by poor prognosis. It is, therefore, of critical importance to elucidate the molecular mechanisms and signaling pathways underlying the progression of early-stage prostate cancer towards CRPC. In this review, we aim to shed light on the role of major signaling pathways including the DNA damage response (DDR) and the developmental Hippo and Notch pathways in prostate tumorigenesis. We recapitulate key evidence demonstrating the crosstalk of those pathways as well as with pivotal prostate cancer-related ‘hubs’ such as AR signaling, and evaluate the clinical impact of those interactions. Moreover, we attempt to identify molecules of the complex DDR–Hippo–Notch interplay comprising potentially novel therapeutic targets in the battle against prostate tumorigenesis.

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Section: The Hippo Pathway In Prostate Cancermentioning

confidence: 99%

Interplay of Developmental Hippo–Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer

Mourkioti

Angelopoulou

Belogiannis

et al. 2022

Cells

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“…Interestingly, the cross talk between these two pathways has been recently reported, highlighting the notion that disruption of their balance will result in tumorigenesis [ 3 ]. Due to the critical roles of the mTORC1 and Hippo pathways under pathobiological conditions, studies and reviews investigating mTORC1 and YAP have been well established [ 4 , 5 ]. However, a summary of the upstream regulation and downstream functions of S6K has still not been provided.…”

Section: Introductionmentioning

confidence: 99%

Beyond controlling cell size: functional analyses of S6K in tumorigenesis

Xie

et al. 2022

Cell Death Dis

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As a substrate and major effector of the mammalian target of rapamycin complex 1 (mTORC1), the biological functions of ribosomal protein S6 kinase (S6K) have been canonically assigned for cell size control by facilitating mRNA transcription, splicing, and protein synthesis. However, accumulating evidence implies that diverse stimuli and upstream regulators modulate S6K kinase activity, leading to the activation of a plethora of downstream substrates for distinct pathobiological functions. Beyond controlling cell size, S6K simultaneously plays crucial roles in directing cell apoptosis, metabolism, and feedback regulation of its upstream signals. Thus, we comprehensively summarize the emerging upstream regulators, downstream substrates, mouse models, clinical relevance, and candidate inhibitors for S6K and shed light on S6K as a potential therapeutic target for cancers.

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“…TAD is essential in the transactivation, PDZ plays an important role in the nuclear translocation of YAP1 (Fig. 1 ) [ 8 , 9 ]. In addition, YAP1/TAZ engage in crosstalk with other cancer-promoting pathways, such as the Notch pathway, MAPK pathway, and Wnt pathway [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

The role of YAP1 in liver cancer stem cells: proven and potential mechanisms

Liu

Liao

et al. 2022

Biomark Res

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YAP1 (Yes-associated protein 1) is one of the principal factors that mediates oncogenesis by acting as a driver of gene expression. It has been confirmed to play an important role in organ volume control, stem cell function, tissue regeneration, tumorigenesis and tumor metastasis. Recent research findings show that YAP1 is correlated with the stemness of liver cancer stem cells, and liver cancer stem cells are closely associated with YAP1-induced tumor initiation and progression. This article reviews the advancements made in research on the mechanisms by which YAP1 promotes liver cancer stem cells and discusses some potential mechanisms that require further study.

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The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer

Cited by 105 publications

References 320 publications

Interplay of Developmental Hippo–Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer

Interplay of Developmental Hippo–Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer

Beyond controlling cell size: functional analyses of S6K in tumorigenesis

The role of YAP1 in liver cancer stem cells: proven and potential mechanisms

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