Metadherin Is a Prognostic Apoptosis Modulator in Mesothelioma Induced via NF- κB-Mediated Signaling.

Metadherin Is a Prognostic Apoptosis Modulator in Mesothelioma Induced via NF-κB-Mediated Signaling. Transl Oncol. 2019 May 01;12(6):859-870 Authors: Zhang L, Singh A, Plaisier C, Pruett N, Ripley RT, Schrump DS, Hoang CD Abstract Therapies against malignant pleural mesothelioma (MPM) have yielded disappointing results, in part, because pathologic mechanisms remain obscure. In searching for rational molecular targets, we identified metadherin (MTDH), a multifunctional gene associated with several tumor types but previously unrecognized in MPM. Cox proportional hazards regression analysis delineated associations between higher MTDH expression and lower patient survival from three independent MPM cohorts (n = 349 patients). Through in vitro assays with overexpression and downregulation constructs in MPM cells, we characterized the role of MTDH. We confirmed in vivo the phenotype of altered MTDH expression in a murine xenograft model. Transcriptional regulators of MTDH were identified by chromatin immunoprecipitation. Overexpression of both MTDH mRNA (12-fold increased) and protein levels was observed in tumor tissues. MTDH stable overexpression significantly augmented proliferation, invasiveness, colony formation, chemoresistance, and an antiapoptosis phenotype, while its suppression showed opposite effects in MPM cells. Interestingly, NF-κB and c-Myc (in a feed-forward loop motif) contributed to modulating MTDH expression. Knock...
Source: Translational Oncology - Category: Cancer & Oncology Authors: Tags: Transl Oncol Source Type: research