&lt;p&gt;Role of Hippo/YAP signaling in irradiation-induced glioma cell apoptosis&lt;/p&gt;

Xu, Xiaofei; Chen, Yan; Wang, Xi; Mu, Xingguo

doi:10.2147/cmar.s210825

Cited by 11 publications

(6 citation statements)

References 33 publications

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“…Several studies have reported that high levels of YAP predict a poor response to RT. YAP activation induces resistance to radiation, while silencing YAP increases sensitivity to RT and potentiates the DNA damage response [ 215 , 216 , 217 ]. Genetic YAP inhibition or treatment with VP sensitizes triple-negative breast cancer cells to RT by targeting the DNA damage response and cell survival pathways [ 218 ].…”

Section: Biochemistry and Translational Properties Of Currently Known Yap Inhibitorsmentioning

confidence: 99%

An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

Morciano

Vezzani

Missiroli

et al. 2021

Cancers

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Yes-associated protein (YAP) has emerged as a key component in cancer signaling and is considered a potent oncogene. As such, nuclear YAP participates in complex and only partially understood molecular cascades that are responsible for the oncogenic response by regulating multiple processes, including cell transformation, tumor growth, migration, and metastasis, and by acting as an important mediator of immune and cancer cell interactions. YAP is finely regulated at multiple levels, and its localization in cells in terms of cytoplasm–nucleus shuttling (and vice versa) sheds light on interesting novel anticancer treatment opportunities and putative unconventional functions of the protein when retained in the cytosol. This review aims to summarize and present the state of the art knowledge about the role of YAP in cancer signaling, first focusing on how YAP differs from WW domain-containing transcription regulator 1 (WWTR1, also named as TAZ) and which upstream factors regulate it; then, this review focuses on the role of YAP in different cancer stages and in the crosstalk between immune and cancer cells as well as growing translational strategies derived from its inhibitory and synergistic effects with existing chemo-, immuno- and radiotherapies.

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Section: Biochemistry and Translational Properties Of Currently Known Yap Inhibitorsmentioning

confidence: 99%

An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

Morciano

Vezzani

Missiroli

et al. 2021

Cancers

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“…In a glioma U251 cell line, irradiation induced cell apoptosis through high expression of c-caspase 3, caspase 3, and Bax. Irradiation also promoted a low expression of YAP and the inactivation of Hippo/YAP signaling through the ubiquitination mediated by RCHY1 ubiquitin ligase, as well as the high expression of Mst1, LATS1, MOB1, and SAVI ( 77 ). Whereas the medulloblastoma cells were irradiated, a YAP high expression was detected, which induced the cell proliferation through high-rise Cyclin D2 (CCND2), and phosphorylated H3 promoted the tumor aggressiveness and tumor recurrence.…”

Section: Tumor Cells Activate Signaling Pathways Involved In Dna-damage Response To Survive Ionizing Radiationmentioning

confidence: 99%

Biological Adaptations of Tumor Cells to Radiation Therapy

Carlos‐Reyes¹,

Muñiz-Lino

Romero-García³

et al. 2021

Front. Oncol.

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Radiation therapy has been used worldwide for many decades as a therapeutic regimen for the treatment of different types of cancer. Just over 50% of cancer patients are treated with radiotherapy alone or with other types of antitumor therapy. Radiation can induce different types of cell damage: directly, it can induce DNA single- and double-strand breaks; indirectly, it can induce the formation of free radicals, which can interact with different components of cells, including the genome, promoting structural alterations. During treatment, radiosensitive tumor cells decrease their rate of cell proliferation through cell cycle arrest stimulated by DNA damage. Then, DNA repair mechanisms are turned on to alleviate the damage, but cell death mechanisms are activated if damage persists and cannot be repaired. Interestingly, some cells can evade apoptosis because genome damage triggers the cellular overactivation of some DNA repair pathways. Additionally, some surviving cells exposed to radiation may have alterations in the expression of tumor suppressor genes and oncogenes, enhancing different hallmarks of cancer, such as migration, invasion, and metastasis. The activation of these genetic pathways and other epigenetic and structural cellular changes in the irradiated cells and extracellular factors, such as the tumor microenvironment, is crucial in developing tumor radioresistance. The tumor microenvironment is largely responsible for the poor efficacy of antitumor therapy, tumor relapse, and poor prognosis observed in some patients. In this review, we describe strategies that tumor cells use to respond to radiation stress, adapt, and proliferate after radiotherapy, promoting the appearance of tumor radioresistance. Also, we discuss the clinical impact of radioresistance in patient outcomes. Knowledge of such cellular strategies could help the development of new clinical interventions, increasing the radiosensitization of tumor cells, improving the effectiveness of these therapies, and increasing the survival of patients.

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“…Hepatocyte necrosis and apoptosis occurs in HCV infection, and it is well documented that Yap downregulation is associated with enhanced apoptosis in normal and neoplastic cells. 65…”

Section: Hcv and Hippo Regulation Via Cd81mentioning

confidence: 99%

Phosphorylated Ezrin (Thr567) Regulates Hippo Pathway and Yes-Associated Protein (Yap) in Liver

Xue

Bhushan

Mars

et al. 2020

The American Journal of Pathology

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The activation of CD81 [the portal of entry of hepatitis C virus (HCV)] by agonistic antibody results in phosphorylation of Ezrin via Syk kinase and is associated with inactivation of the Hippo pathway and increase in yes-associated protein (Yap1). The opposite occurs when glypican-3 or E2 protein of HCV binds to CD81. Hepatocyte-specific glypican-3 transgenic mice have decreased levels of phosphorylated (p)-Ezrin (Thr567) and Yap, increased Hippo activity, and suppressed liver regeneration. The role of Ezrin in these processes has been speculated, but not proved. We show that Ezrin has a direct role in the regulation of Hippo pathway and Yap. Forced expression of plasmids expressing mutant Ezrin (T567D) that mimics p-Ezrin (Thr567) suppressed Hippo activity and activated Yap signaling in hepatocytes in vivo and enhanced activation of pathways of b-catenin and leucine rich repeat containing G proteincoupled receptor 4 (LGR4) and LGR5 receptors. Hepatoma cell lines JM1 and JM2 have decreased CD81 expression and Hippo activity and up-regulated p-Ezrin (T567). NSC668394, a p-Ezrin (Thr567) antagonist, significantly decreased hepatoma cell proliferation. We additionally show that p-Ezrin (T567) is controlled by epidermal growth factor receptor and MET. Ezrin phosphorylation, mediated by CD81-associated Syk kinase, is directly involved in regulation of Hippo pathway, Yap levels, and growth of normal and neoplastic hepatocytes. The finding has mechanistic and potentially therapeutic applications in hepatocyte growth biology, hepatocellular carcinoma, and HCV pathogenesis.

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<p>Role of Hippo/YAP signaling in irradiation-induced glioma cell apoptosis</p>

Cited by 11 publications

References 33 publications

An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

Biological Adaptations of Tumor Cells to Radiation Therapy

Phosphorylated Ezrin (Thr567) Regulates Hippo Pathway and Yes-Associated Protein (Yap) in Liver

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