Transcatheter arterial chemoembolization combined with Hippo/YAP inhibition significantly improve the survival of rats with transplanted hepatocellular carcinoma

Quan, Yi; Li, Zhi; Zhu, Kangshun; Liang, Jundi

doi:10.1186/s12944-021-01486-w

Cited by 7 publications

(4 citation statements)

References 42 publications

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“…Therefore, our result suggested that verteporfin could be used as a preventive drug for the development of HCA and HCC. In fact, a few studies have reported that verteporfin treatment significantly inhibited HCC development (Gavini et al 2019 ; Quan et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Yap signalling regulates ductular reactions in mice with CRISPR/Cas9-induced glycogen storage disease type Ia

Xie

Gao

et al. 2022

Animal Cells and Systems

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Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in the glucose-6-phosphatase (G6Pase, G6pc) enzyme, which catalyses the final step of gluconeogenesis and glycogenolysis. Accumulation of G6pc can lead to an increase in glycogen and development of fatty liver. Ductular reactions refer to the proliferation of cholangiocytes and hepatic progenitors, which worsen fatty liver progress. To date, however, ductular reactions in GSD-Ia remain poorly understood. Here, we studied the development and potential underlying mechanism of ductular reactions in GSD-Ia in mice. We first generated GSD-Ia mice using CRISPR/Cas9 to target the exon 3 region of the G6pc gene. The typical GSD-Ia phenotype in G6pc −/− mice was then analysed using biochemical and histological assays. Ductular reactions in G6pc −/− mice were tested based on the expression of cholangiocytic markers cytokeratin 19 (CK19) and epithelial cell adhesion molecule (EpCAM). Yes-associated protein 1 (Yap) signalling activity was measured using western blot (WB) analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Verteporfin was administered to the G6pc −/− mice to inhibit Yap signalling. The CRISPR/Cas9 system efficiently generated G6pc −/− mice, which exhibited typical GSD-Ia characteristics, including retarded growth, hypoglycaemia, and fatty liver disease. In addition, CK19- and EpCAM-positive cells as well as Yap signalling activity were increased in the livers of G6pc −/− mice. However, verteporfin treatment ameliorated ductular reactions and decreased Yap signalling activity. This study not only improves our understanding of GSD-Ia pathophysiology, but also highlights the potential of novel therapeutic approaches for GSD-Ia such as drug targeting of ductular reactions.

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Section: Discussionmentioning

confidence: 99%

Yap signalling regulates ductular reactions in mice with CRISPR/Cas9-induced glycogen storage disease type Ia

Xie

Gao

et al. 2022

Animal Cells and Systems

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“…In combination with erlotinib, VP reduced invasion, migration and sphere-forming ability. 637 Verteporfin (VP) Liver cancer Verteporfin-mediated inhibition of YAP/TAZ signaling significantly improved transcatheter arterial chemoembolization in transplanted hepatocellular carcinoma (HCC) 638 Verteporfin (VP) Gastric cancer VP disrupts YAP/TAZ-TEAD interaction to decrease the pool of gastric cancer stem cells. 639 Verteporfin (VP) Head and neck cancer (HNSCC) VP suppresses proliferation and metastasis by inhibiting YAP1.…”

Section: Applications In Biomedical Research and Targeted Therapymentioning

confidence: 99%

Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases

Talukdar,

Chatterji

2023

Sig Transduct Target Ther

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Specific cell states in metazoans are established by the symphony of gene expression programs that necessitate intricate synergic interactions between transcription factors and the co-activators. Deregulation of these regulatory molecules is associated with cell state transitions, which in turn is accountable for diverse maladies, including developmental disorders, metabolic disorders, and most significantly, cancer. A decade back most transcription factors, the key enablers of disease development, were historically viewed as ‘undruggable’; however, in the intervening years, a wealth of literature validated that they can be targeted indirectly through transcriptional co-activators, their confederates in various physiological and molecular processes. These co-activators, along with transcription factors, have the ability to initiate and modulate transcription of diverse genes necessary for normal physiological functions, whereby, deregulation of such interactions may foster tissue-specific disease phenotype. Hence, it is essential to analyze how these co-activators modulate specific multilateral processes in coordination with other factors. The proposed review attempts to elaborate an in-depth account of the transcription co-activators, their involvement in transcription regulation, and context-specific contributions to pathophysiological conditions. This review also addresses an issue that has not been dealt with in a comprehensive manner and hopes to direct attention towards future research that will encompass patient-friendly therapeutic strategies, where drugs targeting co-activators will have enhanced benefits and reduced side effects. Additional insights into currently available therapeutic interventions and the associated constraints will eventually reveal multitudes of advanced therapeutic targets aiming for disease amelioration and good patient prognosis.

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“…Moreover, this process could also be driven by YAP1-mediated survival expression [ 102 ]. Inhibition of the Hippo-YAP1 signaling using verteporfin (VP) in combination with transcatheter arterial chemoembolization (TACE), a commonly used therapeutic approach for unresectable HCC, allows reduced tumor burden and improved survival in a transplanted HCC mice model [ 103 ].…”

Section: Hippo Pathway and Other Digestive Malignanciesmentioning

confidence: 99%

Targeting the Hippo Pathway in Gastric Cancer and Other Malignancies in the Digestive System: From Bench to Bedside

et al. 2022

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The Hippo pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration under physiological conditions, and its aberrations have been well studied to promote tumor initiation and progression. Dysregulation of the Hippo tumor suppressor signaling frequently occurs in gastric cancer (GC) and other solid tumors and contributes to cancer development through modulating multiple aspects, including cell proliferation, survival, metastasis, and oncotherapy resistance. In the clinic, Hippo components also possess diagnostic and prognostic values for cancer patients. Considering its crucial role in driving tumorigenesis, targeting the Hippo pathway may greatly benefit developing novel cancer therapies. This review summarizes the current research progress regarding the core components and regulation of the Hippo pathway, as well as the mechanism and functional roles of their dysregulation in gastrointestinal malignancies, especially in GC, and discusses the therapeutic potential of targeting the Hippo pathway against cancers.

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Transcatheter arterial chemoembolization combined with Hippo/YAP inhibition significantly improve the survival of rats with transplanted hepatocellular carcinoma

Cited by 7 publications

References 42 publications

Yap signalling regulates ductular reactions in mice with CRISPR/Cas9-induced glycogen storage disease type Ia

Yap signalling regulates ductular reactions in mice with CRISPR/Cas9-induced glycogen storage disease type Ia

Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases

Targeting the Hippo Pathway in Gastric Cancer and Other Malignancies in the Digestive System: From Bench to Bedside

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