A Promyelocytic Leukemia Protein–Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma

Dvorkina, Maria; Nieddu, Valentina; Chakelam, Shalini; Pezzolo, Annalisa; Cantilena, Sandra; Leite, Ana Paula; Chayka, Olesya; Regad, Tarik; Pistorio, Angela; Sementa, Angela Rita; Virasami, Alex; Barton, Jack; Montano, Ximena; Lechertier, Tanguy; Brindle, Nicola; Morgenstern, Daniel A.; Lebras, Morgane; Burns, Alan J.; Saunders, N.; Hodivala‐Dilke, Kairbaan; Bagella, Luigi; Anderson, John; Sebire, Neil J.; Pistoia, Vito; Sala, Arturo; Salomoni, Paolo

doi:10.1158/1078-0432.ccr-15-2081

Cited by 12 publications

(7 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The frequent deregulation of SCP1 and SCP3 in clear cell renal cell carcinoma and concomitant PML reduction results in mTOR-HIF1 axis activation, thus increasing tumor-associated angiogenesis and tumor burden in Xenograft models [ 153 ]. Alternatively, neuroblastoma contain low level of PML I and PML I-induced expression of thrombospondin-2 (TSP2), a potent angiogenic inhibitor [ 154 ]. Overexpression of PML I in aggressive neuroblastoma cancer cell lines restored inhibition of tumor-associated angiogenesis [ 154 ].…”

Section: Physiological and Pathological Role Of Pmlmentioning

confidence: 99%

“…Alternatively, neuroblastoma contain low level of PML I and PML I-induced expression of thrombospondin-2 (TSP2), a potent angiogenic inhibitor [ 154 ]. Overexpression of PML I in aggressive neuroblastoma cancer cell lines restored inhibition of tumor-associated angiogenesis [ 154 ]. In addition to an intrinsic reduction of PML in cancer cells, it was shown that colorectal cancer cells are capable of reducing PML protein abundance in endothelial cells.…”

Section: Physiological and Pathological Role Of Pmlmentioning

confidence: 99%

See 1 more Smart Citation

PML: Regulation and multifaceted function beyond tumor suppression

Hsu

Kao

2018

Cell Biosci

View full text Add to dashboard Cite

Promyelocytic leukemia protein (PML) was originally identified as a fusion partner of retinoic acid receptor alpha in acute promyelocytic leukemia patients with the (15;17) chromosomal translocation, giving rise to PML–RARα and RARα–PML fusion proteins. A body of evidence indicated that PML possesses tumor suppressing activity by regulating apoptosis, cell cycle, senescence and DNA damage responses. PML is enriched in discrete nuclear substructures in mammalian cells with 0.2–1 μm diameter in size, referred to as alternately Kremer bodies, nuclear domain 10, PML oncogenic domains or PML nuclear bodies (NBs). Dysregulation of PML NB formation results in altered transcriptional regulation, protein modification, apoptosis and cellular senescence. In addition to PML NBs, PML is also present in nucleoplasm and cytoplasmic compartments, including the endoplasmic reticulum and mitochondria-associated membranes. The role of PML in tumor suppression has been extensively studied but increasing evidence indicates that PML also plays versatile roles in stem cell renewal, metabolism, inflammatory responses, neural function, mammary development and angiogenesis. In this review, we will briefly describe the known PML regulation and function and include new findings.

show abstract

Section: Physiological and Pathological Role Of Pmlmentioning

confidence: 99%

Section: Physiological and Pathological Role Of Pmlmentioning

confidence: 99%

PML: Regulation and multifaceted function beyond tumor suppression

Hsu

Kao

2018

Cell Biosci

View full text Add to dashboard Cite

show abstract

“…amplification (Fig. 4a) [44]. For example, treatment with JVG045 at up to 20 μM in the MYCN-non-amplified cell line SHSY5 had no significant effect on cell number (One-way ANOVA, F (5,9) =1.157, p = 0.3989).…”

Section: Jvg045 Inhibits Kpc Mouse-derived Primary Cancer Cell Growthmentioning

confidence: 91%

Rhenium N-heterocyclic carbene complexes block growth of aggressive cancers by inhibiting FGFR- and SRC-mediated signalling

Domenichini

Casari

Simpson

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes. Here we describe the potential anticancer activity of rhenium-based complexes with preclinical efficacy in different types of solid malignancies. Methods Kinase profile assay of rhenium complexes. Toxicology studies using zebrafish. Analysis of the growth of pancreatic cancer cell line-derived xenografts generated in zebrafish and in mice upon exposure to rhenium compounds. Results We describe rhenium complexes which block cancer proliferation in vitro by inhibiting the signalling cascade induced by FGFR and Src. Initially, we tested the toxicity of rhenium complexes in vivo using a zebrafish model and identified one compound that displays anticancer activity with low toxicity even in the high micromolar range. Notably, the rhenium complex has anticancer activity in very aggressive cancers such as pancreatic ductal adenocarcinoma and neuroblastoma. We demonstrate the potential efficacy of this complex via a significant reduction in cancer growth in mouse xenografts. Conclusions Our findings provide a basis for the development of rhenium-based chemotherapy agents with enhanced selectivity and limited side effects compared to standard platinum-based drugs.

show abstract

“…These experiments showed that this compound is particularly active in inhibiting in vitro growth of human neuroblastoma cell lines containing an ampli cation of the MYCN proto-oncogene (Kelly, IMR32, LAN1), while having only a limited effect on neuroblastoma cell lines lacking MYCN ampli cation (Fig. 4A) (44). For example, treatment with JVG045 at up to 20mM in the MYCN-non-ampli ed cell line SHSY5 had no signi cant effect on cell number (One-way ANOVA, F (5,9) =1.157, p=0.3989).…”

Section: Re-nhc Complexes Show Anticancer Activity In Neuroblastoma Cmentioning

confidence: 94%

Rhenium N-heterocyclic carbene complexes block growth of aggressive cancers by inhibiting FGFR- and SRC-mediated signalling

Domenichini

Casari

Simpson

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes. Here we describe the potential anticancer activity of rhenium-based complexes with preclinical efficacy in different types of solid malignancies.Methods: Kinase profile assay of rhenium complexes. Toxicology studies using zebrafish. Analysis of the growth of pancreatic cancer cell line-derived xenografts generated in zebrafish and in mice upon exposure to rhenium compounds.Results: We describe rhenium complexes which block cancer proliferation in vitro by inhibiting the signalling cascade induced by FGFR and Src. Initially, we tested the toxicity of rhenium complexes in vivo using a zebrafish model and identified one compound that displays anticancer activity with low toxicity even in the high micromolar range. Notably, the rhenium complex has anticancer activity in very aggressive cancers such as pancreatic ductal adenocarcinoma and neuroblastoma. We demonstrate the potential efficacy of this complex via a significant reduction in cancer growth in mouse xenografts.Conclusions: Our findings provide a basis for the development of rhenium-based chemotherapy agents with enhanced selectivity and limited side effects compared to standard platinum-based drugs.

show abstract

A Promyelocytic Leukemia Protein–Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma

Cited by 12 publications

References 50 publications

PML: Regulation and multifaceted function beyond tumor suppression

PML: Regulation and multifaceted function beyond tumor suppression

Rhenium N-heterocyclic carbene complexes block growth of aggressive cancers by inhibiting FGFR- and SRC-mediated signalling

Rhenium N-heterocyclic carbene complexes block growth of aggressive cancers by inhibiting FGFR- and SRC-mediated signalling

Contact Info

Product

Resources

About