Τίτλος:
Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic intervention
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Patients with advanced bladder cancer have poor outcomes, indicating a need for more efficient therapeutic approaches. This study characterizes proteomic changes underlying bladder cancer invasion aiming for the better understanding of disease pathophysiology and identification of drug targets. High resolution liquid chromatography coupled to tandem mass spectrometry analysis of tissue specimens from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive bladder cancer (MIBC, stages pT2+) was conducted. Comparative analysis identified 144 differentially expressed proteins between analyzed groups. These included proteins previously associated with bladder cancer and also additional novel such as PGRMC1, FUCA1, BROX and PSMD12, which were further confirmed by immunohistochemistry. Pathway and interactome analysis predicted strong activation in muscle invasive bladder cancer of pathways associated with protein synthesis e.g. eIF2 and mTOR signaling. Knock-down of eukaryotic translation initiation factor 3 subunit D (EIF3D) (overexpressed in muscle invasive disease) in metastatic T24M bladder cancer cells inhibited cell proliferation, migration, and colony formation in vitro and decreased tumor growth in xenograft models. By contrast, knocking down GTP-binding protein Rheb (which is upstream of EIF3D) recapitulated the effects of EIF3D knockdown in vitro, but not in vivo. Collectively, this study represents a comprehensive analysis of NMIBC and MIBC providing a resource for future studies. The results highlight EIF3D as a potential therapeutic target. © Latosinska et al.
Συγγραφείς:
Latosinska, A.
Mokou, M.
Makridakis, M.
Mullen, W.
Zoidakis, J.
Lygirou, V.
Frantzi, M.
Katafigiotis, I.
Stravodimos, K.
Hupe, M.C.
Dobrzynski, M.
Kolch, W.
Merseburger, A.S.
Mischak, H.
Roubelakis, M.G.
Vlahou, A.
Περιοδικό:
OncoTargets and therapy
Εκδότης:
Impact Journals, LLC
Λέξεις-κλειδιά:
BROX protein; eukaryotic translation initiation factor 3 subunit D; FUCA1 protein; initiation factor 3; PGRMC1 protein; PSMD12 protein; tumor protein; unclassified drug, animal experiment; animal model; Article; cell migration; cell proliferation; clinical article; colony formation; controlled study; disease association; down regulation; human; human tissue; immunohistochemistry; intervention study; liquid chromatography-mass spectrometry; male; mouse; muscle invasive bladder cancer; non muscle invasive bladder cancer; nonhuman; protein analysis; protein expression; protein protein interaction; protein targeting; proteomics; tumor invasion; upregulation
DOI:
10.18632/oncotarget.17279
