Cancers, Vol. 12, Pages 904: The Receptor Tyrosine Kinase RON and Its Isoforms as Therapeutic Targets in Ewing Sarcoma:
Cancers, Vol. 12, Pages 904: The Receptor Tyrosine Kinase RON and Its Isoforms as Therapeutic Targets in Ewing Sarcoma
Cancers doi: 10.3390/cancers12040904
Authors:
Philipp Berning
Carolin Hennemann
Claudia Tulotta
Christiane Schaefer
Birgit Lechtape
Marc Hotfilder
Yassmine El Gourari
Heribert Jürgens
Ewa Snaar-Jagalska
Georg Hempel
Uta Dirksen
Jenny Potratz
The receptor tyrosine kinase (RTK) RON is linked to an aggressive metastatic phenotype of carcinomas. While gaining interest as a therapeutic target, RON remains unstudied in sarcomas. In Ewing sarcoma, we identified RON among RTKs conferring resistance to insulin-like growth factor-1 receptor (IGF1R) targeting. Therefore, we explored RON in pediatric sarcoma cell lines and an embryonic Tg(kdrl:mCherry) zebrafish model, using an shRNA-based approach. To examine RON–IGF1R crosstalk, we employed the clinical-grade monoclonal antibody IMC-RON8, alone and together with the IGF1R-antibody IMC-A12. RON silencing demonstrated functions in vitro and in vivo, particularly within micrometastatic cellular capacities. Signaling studies revealed a unidirectional IGF1-mediated cross-activation of RON. Yet, IMC-A12 failed to sensitize cells to IMC-RON8, suggesting additional mechanisms of RON activation. Here, RT-PCR revealed that childhood sarcomas express short-form RON, an isoform resistant to antibody-mediated targeting. Interestingly, in contrast to carcinomas, treatment with DNA methyltransferase inhibitor did not diminish but increased short-form RON expression. Thus, this first report supports a role for RON in the metastatic progression of Ewing sarcoma. While principal molecular functions appear transferrable between carcinomas, Ewing sarcoma and possibly more common sarcoma subtypes, RON highlights that specific regulations of cellular networks and isoforms require better understanding to successfully transfer targeting strategies.
Medicine RSS-Feeds by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com
Πληροφορίες
Τρίτη 7 Απριλίου 2020
Cancers, Vol. 12, Pages 904: The Receptor Tyrosine Kinase RON and Its Isoforms as Therapeutic Targets in Ewing Sarcoma
Αναρτήθηκε από
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
στις
11:23 μ.μ.
Ετικέτες
00302841026182,
00306932607174,
alsfakia@gmail.com,
Anapafseos 5 Agios Nikolaos 72100 Crete Greece,
Medicine by Alexandros G. Sfakianakis,
Telephone consultation 11855 int 1193
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Αρχειοθήκη ιστολογίου
-
►
2023
(366)
- ► Φεβρουαρίου (184)
- ► Ιανουαρίου (182)
-
►
2022
(2814)
- ► Δεκεμβρίου (182)
- ► Σεπτεμβρίου (213)
- ► Φεβρουαρίου (264)
- ► Ιανουαρίου (262)
-
►
2021
(3815)
- ► Δεκεμβρίου (229)
- ► Σεπτεμβρίου (276)
- ► Φεβρουαρίου (64)
-
▼
2020
(5754)
- ► Δεκεμβρίου (401)
- ► Σεπτεμβρίου (365)
-
▼
Απριλίου
(843)
-
▼
Απρ 07
(151)
- Pediatric septal dysembryoplastic neuroepithelial ...
- Pathogenesis of peritumoral hyperexcitability in a...
- Malignant transformation rate of oral leukoplakia-...
- Olaparib for advanced breast cancer.
- lncRNA and mRNA signature for prognosis prediction...
- DHRS12 inhibits the proliferation and metastasis o...
- Whole lung irradiation for completely responding p...
- ENGINE: a Phase III randomized placebo controlled ...
- Quantification of heterogeneity to classify benign...
- Kappa opioids modulate hedgehog signaling to atten...
- Nobiletin Attenuates DSS-Induced Intestinal Barrie...
- Small molecules, big effects- microbial metabolite...
- Network-based metabolic characterization of renal ...
- Aggregates of RNA Binding Proteins and ER Chaperon...
- HIV-1 infection and latency-reversing agents bryos...
- Comparison of the effects of polynucleotide and hy...
- Therapeutic outcome of diphencyprone and its corre...
- Efficacy of non-surgical treatments for androgenet...
- Efficacy of brodalumab in the treatment of scalp a...
- Development of the Japanese version of the Other A...
- Systematic characterization of non-coding RNAs in ...
- Generation of an Enteric Smooth Muscle Cell Line f...
- Amyloid-β Causes Mitochondrial Dysfunction via a C...
- Parental metabolic syndrome epigenetically reprogr...
- Comparison of Methods To Collect Fecal Samples for...
- Prevention of Decompression Sickness by Novel Arti...
- Leptin receptor-expressing neuron Sh2b1 supports s...
- Biomarkers for Alzheimer's disease-preparing for a...
- Network mechanisms and dysfunction within an integ...
- Comparative physiology and efficacy of atropine an...
- Biomonitoring of Bis(2-ethylhexyl)phthalate (DEHP)...
- Definition of locally recurrent head and neck squa...
- Long-term electrophysiological assessment after hy...
- Tension pneumocephalus after skull base surgery. A...
- Antioxidant Micronutrients and Essential Fatty Aci...
- Critically ill patients with COVID-19 in Hong Kong...
- The role of the paediatrician in caring for childr...
- Urban Particles Elevated Streptococcus pneumoniae ...
- Point of care testing of Influenza A/B and RSV in ...
- Immunoactive preparations and regulatory responses...
- Anesthesia timing for children undergoing therapeu...
- Safety and immunogenicity of a parenteral trivalen...
- Human bocavirus 1 and 2 genotypes detected in youn...
- Hospital-Acquired Viral Respiratory Tract Infectio...
- Epidemiology, virology, and clinical features of s...
- Role of cinnamon oil against acetaminophen overdos...
- The pro-convulsant effects of diazinon low dose in...
- Drugs frequently involved in inducing hypersensiti...
- Cholinergic agonists inhibit proliferation of huma...
- Alteration of liver immunity by increasing inflamm...
- Laquinimod inhibits MMP+ induced NLRP3 inflammasom...
- Hepatoprotective effects of melatonin and celecoxi...
- Bilateral total deafness after preparation of wild...
- Evaluation of a low-dose protocol for Cone-Beam co...
- Straighten your back! Self-correction posture and ...
- Cellular immunotherapy: a clinical state-of-the-ar...
- First detection and genotyping of Enterocytozoon b...
- Juglanin alleviates bleomycin-induced lung injury ...
- Follow-up of percutaneous microwave (MW) ablation ...
- Circular RNAs and their participation in stemness ...
- The impact of rattlesnake venom on mice cerebellum...
- Embolization of a Superior Thyroid Artery Hemorrha...
- Muscle-specific modulation of indirect inputs to p...
- Modulation of soleus muscle H-reflexes and ankle m...
- Upper canine response to rapid maxillary expander ...
- Comparative Proteome Analyses of Ureteropelvic Jun...
- Comparing the trueness of seven intraoral scanners...
- Influence of cavity depth and restoration of non-c...
- Technology at the service of surgery in a new tech...
- Modeling the effect of brain growth on cranial bon...
- An adult patient presenting with right unilateral ...
- Cancers, Vol. 12, Pages 894: An Updated Perspectiv...
- Cancers, Vol. 12, Pages 893: Mechanisms of Resista...
- Cancers, Vol. 12, Pages 896: Detection of Circulat...
- Cancers, Vol. 12, Pages 895: Differentially Methyl...
- Cancers, Vol. 12, Pages 898: The Interplay of Dysr...
- Cancers, Vol. 12, Pages 897: Comparison between Y9...
- Cancers, Vol. 12, Pages 899: Transport Metabolons ...
- Cancers, Vol. 12, Pages 902: Drug Development Targ...
- Cancers, Vol. 12, Pages 900: The n-10 Fatty Acids ...
- Cancers, Vol. 12, Pages 901: Development of a Mode...
- Cancers, Vol. 12, Pages 904: The Receptor Tyrosine...
- Cancers, Vol. 12, Pages 903: Role of DNA Damage Re...
- Cancers, Vol. 12, Pages 905: ARID1A Regulates Tran...
- Expression of the immune checkpoint VISTA in breas...
- Defining biomarkers to predict symptoms in subject...
- A genome-wide association study implicates the BMP...
- Human genetics of Buruli ulcer
- The Supernatant of Tonsil-Derived Mesenchymal Stem...
- The Plasma Soluble Urokinase Plasminogen Activator...
- Assessment of Arf6 Deletion in PLB-985 Differentia...
- Quantitative proteomic landscape of metaplastic br...
- In situ supramolecular polymerization-enhanced sel...
- Quantitative proteomic landscape of metaplastic br...
- TrkB-expressing paraventricular hypothalamic neuro...
- A prospective longitudinal study of clinical outco...
- A prospective longitudinal study of clinical outco...
- Validity and Reliability of Chronic Otitis Media Q...
- An Objective Ergonomic Risk Assessment of Surgeons...
- Predictive value of non-specific bronchial challen...
-
▼
Απρ 07
(151)
- ► Φεβρουαρίου (754)
- ► Ιανουαρίου (894)
-
►
2019
(146)
- ► Δεκεμβρίου (19)
- ► Σεπτεμβρίου (54)
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου