The Hippo Pathway and Viral Infections

Wang, Zhilong; Lu, Wanhang; Zhang, Shujun; Feng, Zhiyong; Jin, Zhigang; Zhao, Tiejun

doi:10.3389/fmicb.2019.03033

Cited by 53 publications

(50 citation statements)

References 87 publications

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“…Accumulating evidence shows that the Hippo/YAP signaling pathway plays critical roles in a wide range of biological processes, including cell proliferation, apoptosis, and tumorigenesis ( 13 , 14 , 20 ). Dysregulation of YAP protein, the key factor in the Hippo pathway, has been implicated in viral transformation ( 21 ). Examples include hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), Epstein–Barr virus, and Kaposi sarcoma-associated herpesvirus ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence shows that a variety of human viruses exert their carcinogenic function via the Hippo pathway ( 21 ). Known mechanisms of Hippo dysregulation in virus-infected cells include 1) up-regulation of YAP expression through activating its promoter ( 22 – 24 ), 2) inhibition of proteasome-dependent degradation of YAP protein ( 25 , 26 ), 3) inhibition of YAP phosphorylation to increase nuclear localization ( 26 , 27 ), and 4) suppression of the Hippo pathway through regulating the kinase activity of MST1/2 or LATS1/2 ( 28 ).…”

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confidence: 99%

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HTLV-1 activates YAP via NF-κB/p65 to promote oncogenesis

Zhao

Wang

Fang

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection. HTLV-1 exerts its oncogenic functions by interacting with signaling pathways involved in cell proliferation and transformation. Dysregulation of the Hippo/YAP pathway is associated with multiple cancers, including virus-induced malignancies. In the present study, we observe that expression of YAP, which is the key effector of Hippo signaling, is elevated in ATL cells by the action of the HTLV-1 Tax protein. YAP transcriptional activity is remarkably enhanced in HTLV-1–infected cells and ATL patients. In addition, Tax activates the YAP protein via a mechanism involving the NF-κB/p65 pathway. As a mechanism for this cross talk between the Hippo and NF-κB pathways, we found that p65 abrogates the interaction between YAP and LATS1, leading to suppression of YAP phosphorylation, inhibition of ubiquitination-dependent degradation of YAP, and YAP nuclear accumulation. Finally, knockdown of YAP suppresses the proliferation of ATL cells in vitro and tumor formation in ATL-engrafted mice. Taken together, our results suggest that p65-induced YAP activation is essential for ATL pathogenesis and implicate YAP as a potential therapeutic target for ATL treatment.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

HTLV-1 activates YAP via NF-κB/p65 to promote oncogenesis

Zhao

Wang

Fang

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Since the MAPK pathway plays a vital role in releasing pro-inflammatory cytokines (e.g., IL6 ) associated with myocardial dysfunction and acute lung injury, targeted inhibition of this pathway could attenuate SARS-CoV-2 infection [ 24 ]. In addition, therapeutic inhibition of the Hippo pathway component may provide a potential value for antiviral treatment [ 25 ]. Furthermore, it found that in COVID-19 patients, TGFβ stimulates the WNT/β-catenin pathway, leading to an increased risk of pulmonary diseases.…”

Section: Discussionmentioning

confidence: 99%

Comparisons of the immunological landscape of COVID-19 patients based on sex and disease severity by multi-omics analysis

Zhang

Abdelrahman

Liu

et al. 2022

Chemico-Biological Interactions

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Objective To determine the differences in the immune response against SARS-CoV-2 infection of patients based on sex and disease severity. Methods We used an analytical framework of 382 transcriptional modules and multi-omics analyses to discriminate COVID-19 patients based on sex and disease severity. Results Male and female patients overexpressed modules related to the innate immune response. The expression of modules related to the adaptive immune response showed lower enrichment levels in males than females. Inflammation modules showed ascending overexpression in male and female patients, while a higher level was observed in severe female patients. Moderate female patients demonstrated significant overexpression to interferon, cytolytic lymphocyte, T & B cells, and erythrocytes modules. Moderate female patients showed a higher adaptive immune response than males matched group. Pathways involved in metabolism dysregulation and Hippo signaling were upregulated in females than in male patients. Females and moderate cases showed higher levels of metabolic dysregulation. Conclusions The immune landscape in COVID-19 patients was noticeably different between the sexes, and these differences may highlight disease vulnerability in males. This study suggested that certain treatments that increase or decrease the immune responses to SARS-CoV-2 might be necessary for male and female patients at certain disease stages.

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“…Meanwhile, in breast cancer, EBV infection also causes inactivation of the Hippo signaling pathway 62 . It also has been reported that when hepatitis C virus (HCV), infectious mollusc virus (MCV), mouse polyomavirus (MupyV), Kaposi Sarcoma-associated herpesvirus (KSHV), Zika virus (ZIKA) affecting host cells, the increase of YAP/TAZ expression activity could be found 63 .…”

Section: The Upstream Regulatory Network Of the Hippo Signaling Pathwaymentioning

confidence: 99%

The regulatory networks of the Hippo signaling pathway in cancer development

et al. 2021

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The Hippo signaling pathway is a relatively young tumor-related signaling pathway. Although it was discovered lately, research on it developed rapidly. The Hippo signaling pathway is closely relevant to the occurrence and development of tumors and the maintenance of organ size and other biological processes. This manuscript focuses on YAP, the core molecule of the Hippo signaling pathway, and discussion the upstream and downstream regulatory networks of the Hippo signaling pathway during tumorigenesis and development. It also summarizes the relevant drugs involved in this signaling pathway, which may be helpful to the development of targeted drugs for cancer therapy.

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The Hippo Pathway and Viral Infections

Cited by 53 publications

References 87 publications

HTLV-1 activates YAP via NF-κB/p65 to promote oncogenesis

HTLV-1 activates YAP via NF-κB/p65 to promote oncogenesis

Comparisons of the immunological landscape of COVID-19 patients based on sex and disease severity by multi-omics analysis

The regulatory networks of the Hippo signaling pathway in cancer development

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