Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Canine malignant melanoma, a significant cause of mortality in domestic dogs, is a powerful comparative model for human melanoma, but little is known about its genetic etiology. We mapped the genomic landscape of canine melanoma through multi-platform analysis of 37 tumors (31 mucosal, 3 acral, 2 cutaneous, and 1 uveal) and 17 matching constitutional samples including long- and short-insert whole genome sequencing, RNA sequencing, array comparative genomic hybridization, single nucleotide polymorphism array, and targeted Sanger sequencing analyses. We identified novel predominantly truncating mutations in the putative tumor suppressor gene PTPRJ in 19% of cases. No BRAF mutations were detected, but activating RAS mutations (24% of cases) occurred in conserved hotspots in all cutaneous and acral and 13% of mucosal subtypes. MDM2 amplifications (24%) and TP53 mutations (19%) were mutually exclusive. Additional low-frequency recurrent alterations were observed amidst low point mutation rates, an absence of ultraviolet light mutational signatures, and an abundance of copy number and structural alterations. Mutations that modulate cell proliferation and cell cycle control were common and highlight therapeutic axes such as MEK and MDM2 inhibition. This mutational landscape resembles that seen in BRAF wild-type and sun-shielded human melanoma subtypes. Overall, these data inform biological comparisons between canine and human melanoma while suggesting actionable targets in both species.
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PMID:Somatic inactivating PTPRJ mutations and dysregulated pathways identified in canine malignant melanoma by integrated comparative genomic analysis. 3018 88

CD148 is a member of the receptor-type protein tyrosine phosphatase family encoded by the PTPRJ gene and has controversial impacts on cancers. In this study, we investigated the clinical significance of CD148 in gastric cancer and the possible mechanisms. Suppressed CD148 expression indicated adverse pathological features and poor outcomes in gastric cancer patients. CD148 overexpression impeded tumor proliferation, motility, and invasiveness, while CD148 knock-down or knockout promoted the ability of gastric cancer cells to grow and metastasize in vitro and in vivo. Mechanistically, CD148 negatively regulated EGFR phosphorylation of multiple tyrosine residues, including Y1173, Y1068, and Y1092, and remarkably inhibited downstream PI3K/AKT and MEK/ERK pathways. In silico analysis revealed that gene deletions or missense/truncated mutations of PTPRJ gene rarely occurred in gastric cancers. Instead, a 3' UTR-specific methylation might regulate CD148 expression, and the potential regulators were TET2 and TET3. Collectively, our results suggest that CD148 is a convincing prognostic marker as well as a potential therapeutic target for gastric cancer.
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PMID:CD148 Serves as a Prognostic Marker of Gastric Cancer and Hinders Tumor Progression by Dephosphorylating EGFR. 3220 37