PRAME/EZH2-Mediated Regulation of TRAIL: A New Target for Cancer Therapy

Carvalho, Daniel D De; Mello, Bárbara Piffero; Pereira, Welbert Oliveira; Amarante-Mendes, Gustavo P.

doi:10.2174/156652413804810727

Cited by 22 publications

(19 citation statements)

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“…Although the function of PRAME in tumourigenesis has not yet been fully elucidated, it is known that PRAME can bind to the retinoic acid receptor in the presence of retinoic acid and thereby repress retinoic acid receptor signalling and TRAIL expression, causing cell proliferation and preventing apoptosis and cell‐cycle arrest . The function of NY‐ESO‐1 in tumourigenesis also remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Cancer‐testis antigens PRAME and NY‐ESO‐1 correlate with tumour grade and poor prognosis in myxoid liposarcoma

Iura

Kohashi

Hotokebuchi

et al. 2015

The Journal of Pathology CR

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Myxoid liposarcoma is the second most common liposarcoma. Although myxoid liposarcoma is relatively chemosensitive and thus a good candidate for chemotherapy, cases with relapsed or metastatic disease still have poor outcome. Here, we performed a gene microarray analysis to compare the gene expression profiles in six clinical myxoid liposarcoma samples and three normal adipose tissue samples, and to identify molecular biomarkers that would be useful as diagnostic markers or treatment targets in myxoid liposarcoma. This showed that the cancer‐testis antigen PRAME was up‐regulated in myxoid liposarcoma. We then performed immunohistochemical, western blotting and real‐time polymerase chain reaction analyses to quantify the expression of PRAME and another cancer‐testis antigen, NY‐ESO‐1, in clinical samples of myxoid liposarcoma (n = 93), dedifferentiated (n = 46), well‐differentiated (n = 32) and pleomorphic liposarcomas (n = 14). Immunohistochemically, positivity for PRAME and NY‐ESO‐1 was observed in 84/93 (90%) and 83/93 (89%) of the myxoid liposarcomas, and in 20/46 (43%) and 3/46 (7%) of the dedifferentiated, 3/32 (9%) and 1/32 (3%) of the well‐differentiated and 7/14 (50%) and 3/21 (21%) of the pleomorphic liposarcomas, respectively. High immunohistochemical expression of PRAME and/or NY‐ESO‐1 was significantly correlated with tumour diameter, the existence of tumour necrosis, a round‐cell component of >5%, higher histological grade and advanced clinical stage. High PRAME and NY‐ESO‐1 expression correlated significantly with poor prognosis in a univariate analysis. The myxoid liposarcomas showed significantly higher protein and mRNA expression levels of PRAME and NY‐ESO‐1 (CTAG1B) than the other liposarcomas. In conclusion, PRAME and NY‐ESO‐1 (CTAG1B) were expressed in the vast majority of myxoid liposarcomas, and their high‐level expression correlated with tumour grade and poor prognosis. Our results support the potential use of PRAME and NY‐ESO‐1 as ancillary parameters for differential diagnosis and as prognostic biomarkers, and indicate that the development of immunotherapy against these cancer‐testis antigens in myxoid liposarcoma would be warranted.

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Section: Discussionmentioning

confidence: 99%

Cancer‐testis antigens PRAME and NY‐ESO‐1 correlate with tumour grade and poor prognosis in myxoid liposarcoma

Iura

Kohashi

Hotokebuchi

et al. 2015

The Journal of Pathology CR

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“…These data demonstrate that use of systems biology and network modeling is revealing a vast new set of intracellular proteins that could be therapeutically targeted to increase TRAIL-induced apoptosis. Interestingly enough, TRAIL expression can be inhibited by PRAME/EZH2 complex in CML (chronic myeloid leukemia) patients, and restoration of TRAIL expression enhanced sensitivity to chemotherapeutic drugs (De Carvalho et al, 2011; De Carvalho et al, 2013). …”

Section: Resistance To Trail—mediated Cell Deathmentioning

confidence: 99%

“…Forth, TRAIL deficiency in mice was associated with increased carcinogen-induced tumorigenesis and metastasis, particularly to the liver (Cretney et al, 2002; Sedger et al, 2002). Fifth, TRAIL expression is down regulated in a variety of human cancers and restoration of TRAIL expression enhances in vitro tumor sensitivity to chemotherapeutic drugs (De Carvalho et al, 2011, 2013). …”

Section: Introductionmentioning

confidence: 99%

Therapeutic applications of TRAIL receptor agonists in cancer and beyond

Amarante-Mendes

Griffith

2015

Pharmacology & Therapeutics

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TRAIL/Apo-2L is a member of the TNF superfamily first described as an apoptosis-inducing cytokine in 1995. Similar to TNF and Fas ligand, TRAIL induces apoptosis in caspase-dependent manner following TRAIL death receptor trimerization. Because tumor cells were shown to be particularly sensitive to this cytokine while normal cells/tissues proved to be resistant along with being able to synthesize and release TRAIL, it was rapidly appreciated that TRAIL likely served as one of our major physiologic weapons against cancer. In line with this, a number of research laboratories and pharmaceutical companies have attempted to exploit the ability of TRAIL to kill cancer cells by developing recombinant forms of TRAIL or TRAIL receptor agonists (e.g., receptor-specific mAb) for therapeutic purposes. In this review article we will describe the biochemical pathways used by TRAIL to induce different cell death programs. We will also summarize the clinical trials related to this pathway and discuss possible novel uses of TRAIL-related therapies. In recent years, the physiological importance of TRAIL has expanded beyond being a tumoricidal molecule to one critical for a number of clinical settings — ranging from infectious disease and autoimmunity to cardiovascular anomalies. We will also highlight some of these conditions where modulation of the TRAIL/TRAIL receptor system may be targeted in the future.

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“…Because of the low sensitivity and high toxicity of chemotherapy drugs, the identification of a new treatment for gastric cancer is urgent. Recombinant TRAIL has been tested in clinical trials and has shown promising anti‐tumor activities with mild side effects . However, resistance to TRAIL is a major clinical challenge in gastric cancer cells, leading to the failure of treatment, poor prognosis, and reduced cancer patient survival .…”

Section: Discussionmentioning

confidence: 99%

Antitumor Effect of Periplocin in TRAIL‐Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2‐EGR1 pathway

Zhao

Huang³

et al. 2019

Molecular Carcinogenesis

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Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), a member of the tumor necrosis factor family, induces apoptosis in a variety of cancer cells. However, gastric cancer (GC) cells are insensitive to TRAIL usually. In the previous study, we showed that Periplocin could induce apoptosis in GC cells via the activation of ERK1/2‐EGR1 pathway. In the present study, we have shown that the combination of Periplocin and TRAIL had a greater inhibitory effect on gastric cancer cell viability in vitro and in vivo than Periplocin or TRAIL alone. Through upregulating the expression of DR4 and DR5 at transcriptional and protein levels, Periplocin enhanced the sensitivity of gastric cancer cells to TRAIL. Furthermore, enhanced activity of ERK1/2‐EGR1 pathway was responsible for upregulating of DR4 and DR5 uponPeriplocin treatment, subsequently reducing the expression of Mcl‐1 and Bcl2 and activating Bid and caspase‐3/8. Collectively, these data implied that Periplocin might act as a sensitizer of TRAIL and could be a potential strategy for the treatment of GC.

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PRAME/EZH2-Mediated Regulation of TRAIL: A New Target for Cancer Therapy

Cited by 22 publications

References 0 publications

Cancer‐testis antigens PRAME and NY‐ESO‐1 correlate with tumour grade and poor prognosis in myxoid liposarcoma

Cancer‐testis antigens PRAME and NY‐ESO‐1 correlate with tumour grade and poor prognosis in myxoid liposarcoma

Therapeutic applications of TRAIL receptor agonists in cancer and beyond

Antitumor Effect of Periplocin in TRAIL‐Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2‐EGR1 pathway

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