The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma

Yang, Wen‐Hsuan; Ding, Chien‐Kuang Cornelia; Sun, Tianai; Hsu, David S.; Ashley, Jen-Tsan

doi:10.2139/ssrn.3316797

Cited by 56 publications

(78 citation statements)

References 45 publications

(61 reference statements)

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“…In the report of Yang and co-workers it has been shown that active and nuclearlocalized TAZ regulates epithelial membrane protein 1 (EMP1) expression, which in turn increases NAD(P)H oxidase 4 (NOX4) expression in RCC. NOX4 is a ROSproducing enzyme whose involvement in lipid peroxidation has been noted in the previous studies 73,74 . An interesting observation of this study is that erastin did not affect GSH level in the TAZ knockout cells expressing low level of NOX4 (but did in WT cells with higher amount of NOX4), thus indicating that most of GSH reducing power in RCC has been used for amelioration of the NOX4dependent oxidative damage 73 .…”

Section: Hippo Pathway and Lipid Peroxidesmentioning

confidence: 74%

“…Hippo pathway involvement in the ferroptosis resistance: the role of YAP/TAZ First papers dealing with the mechanistic insights of density-based resistance to ferroptosis appeared quite recently and suggested the Hippo pathway as a major player this event [70][71][72][73][74] . In brief, the main role of the highly conserved Hippo pathway is to restrict tissue growth in adults and to modulate cell proliferation, differentiation, and migration in developing organs, in response to different signals including cell-to-cell contact, cell polarity, energy status, mechanical clues, etc.…”

Section: Cell-to-cell Contactmentioning

confidence: 99%

“…This further provides evidence for the functional link between E-cadherin, Hippo pathway and ferroptosis. Another study done on the highly ferroptosis-sensitive renal cell carcinoma (RCC) came to the same functional link, although focusing on the other Hippo pathway regulator-TAZ 73 .…”

Section: Cell-to-cell Contactmentioning

confidence: 99%

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Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

et al. 2020

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Contextualisation of the new type of cell death called “ferroptosis” opened a completely new avenue for the development of anti-cancer therapies. Cumulative fundamental research dating back to the mid-20th century, crowned by the extraordinary work of the group led by Dr. Stockwell from Columbia University in 2012, finally got its candidature to be applied in the clinical settings. Although the potential for clinical importance is undoubtedly growing every day, as showed by the increasing number of papers dealing with ferroptosis and its applications, long experience of cancer research and treatment taught us that caution is still necessary. The plasticity of the tumour cells, particularly acute, along with its involvement in the resistance mechanisms, that have been seen, to greater or lesser extent, for almost all currently used therapies, represents the biggest fascinations in biomedical research field and also the biggest challenge to achieving cures in cancer patients. Accordingly, the main features of fundamental research have to be vigilance and anticipation. In this review, we tried to summarize the literature data, accumulated in the past couple of years, which point out the pitfalls in which “ferroptosis inducers” can fall if used prematurely in the clinical settings, but at the same time can provide a great advantage in the exhausting battle with cancer resistance. This is the first comprehensive review focusing on the effects of the cell-to-cell contact/interplay in the development of resistance to ferroptosis, while the contribution of cell-born factors has been summarized previously so here we just listed them.

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Section: Hippo Pathway and Lipid Peroxidesmentioning

confidence: 74%

Section: Cell-to-cell Contactmentioning

confidence: 99%

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Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

et al. 2020

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“…However, although we are glad that the propagation of cell death may contribute to cancer therapy, another study reported that a high cell density (>80% confluency) makes cells less sensitive to erastin‐induced ferroptosis via the Hippo pathway that regulates TAZ‐EMP1‐NOX4 axis (Figure ) . In addition, recent research has demonstrated that cell–cell contacts inhibit erastin‐induced ferroptosis and t‐BuOOH‐induced ferroptosis by decreasing basal and lipid peroxidation.…”

Section: Progress In Ferroptosis Application In Cancer Therapymentioning

confidence: 99%

“…Recently, ferroptosis has become a hot topic in a variety of diseases, especially cancer therapy . For instance, new findings reveal that cell density can affect the sensitivity to ferroptosis, and another study showed that ferroptosis can spread through cell populations in a wave‐like manner . These factors should be considered when ferroptosis is applied to cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis: Final destination for cancer?

et al. 2020

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Ferroptosis is a recently defined, non‐apoptotic, regulated cell death (RCD) process that comprises abnormal metabolism of cellular lipid oxides catalysed by iron ions or iron‐containing enzymes. In this process, a variety of inducers destroy the cell redox balance and produce a large number of lipid peroxidation products, eventually triggering cell death. However, in terms of morphology, biochemistry and genetics, ferroptosis is quite different from apoptosis, necrosis, autophagy‐dependent cell death and other RCD processes. A growing number of studies suggest that the relationship between ferroptosis and cancer is extremely complicated and that ferroptosis promises to be a novel approach for the cancer treatment. This article primarily focuses on the mechanism of ferroptosis and discusses the potential application of ferroptosis in cancer therapy.

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Metabolomic effects of androgen deprivation therapy treatment for prostate cancer

Chi

Lin

Tolstikov³

et al. 2020

Cancer Medicine

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Androgen deprivation therapy (ADT) is the main treatment strategy for men with metastatic prostate cancer (PC). However, ADT is associated with various metabolic disturbances, including impaired glucose tolerance, insulin resistance and weight gain, increasing risk of diabetes and cardiovascular death. Much remains unknown about the metabolic pathways and disturbances altered by ADT and the mechanisms. We assessed the metabolomic effects of ADT in the serum of 20 men receiving ADT. Sera collected before (baseline), 3 and 6 months after initiation of ADT was used for the metabolomics and lipidomics analyses. The ADT‐associated metabolic changes were identified by univariable and multivariable statistical analysis, ANOVA, and Pearson correlation. We found multiple key changes. First, ADT treatments reduced the steroid synthesis as reflected by the lower androgen sulfate and other steroid hormones. Greater androgen reduction was correlated with higher serum glucose levels, supporting the diabetogenic role of ADT. Second, ADT consistently decreased the 3‐hydroxybutyric acid and ketogenesis. Third, many acyl‐carnitines were reduced, indicating the effects on the fatty acid metabolism. Fourth, ADT was associated with a corresponding reduction in 3‐formyl indole (a.k.a. indole‐3‐carboxaldehyde), a microbiota‐derived metabolite from the dietary tryptophan. Indole‐3‐carboxaldehyde is an agonist for the aryl hydrocarbon receptor and regulates the mucosal reactivity and inflammation. Together, these ADT‐associated metabolomic analyses identified reduction in steroid synthesis and ketogenesis as prominent features, suggesting therapeutic potential of restricted ketogenic diets, though this requires formal testing. ADT may also impact the microbial production of indoles related to the immune pathways. Future research is needed to determine the functional impact and underlying mechanisms to prevent ADT‐linked comorbidities and diabetes risk.

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The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma

Cited by 56 publications

References 45 publications

Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

Ferroptosis: Final destination for cancer?

Metabolomic effects of androgen deprivation therapy treatment for prostate cancer

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