Proteomic analysis of STEAP1 knockdown in human LNCaP prostate cancer cells.

Autor: Rocha SM; CICS-UBI-Health Sciences Research Center, Universidade da Beira Interior, 6201-506 Covilhã, Portugal., Santos FM; CICS-UBI-Health Sciences Research Center, Universidade da Beira Interior, 6201-506 Covilhã, Portugal; Functional Proteomics Laboratory, Centro Nacional de Biotecnología (CNB-CSIC), Calle Darwin 3, Campus de Cantoblanco, 28029 Madrid, Spain., Socorro S; CICS-UBI-Health Sciences Research Center, Universidade da Beira Interior, 6201-506 Covilhã, Portugal., Passarinha LA; CICS-UBI-Health Sciences Research Center, Universidade da Beira Interior, 6201-506 Covilhã, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2819-516 Caparica, Portugal; UCIBIO-Applied Molecular Biosciences Unit, Department of Chemistry, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2819-516 Caparica, Portugal; Laboratório de Fármaco-Toxicologia-UBIMedical, Universidade da Beira Interior, 6201-284 Covilhã, Portugal., Maia CJ; CICS-UBI-Health Sciences Research Center, Universidade da Beira Interior, 6201-506 Covilhã, Portugal. Electronic address: cmaia@fcsaude.ubi.pt.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2023 Oct; Vol. 1870 (7), pp. 119522. Date of Electronic Publication: 2023 Jun 12.
DOI: 10.1016/j.bbamcr.2023.119522
Abstrakt: Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. The six transmembrane epithelial antigen of the prostate 1 (STEAP1) protein is overexpressed in several types of human tumors, particularly in PCa. Our research group has demonstrated that STEAP1 overexpression is associated with PCa progression and aggressiveness. Therefore, understanding the cellular and molecular mechanisms triggered by STEAP1 overexpression will provide important insights to delineate new strategies for PCa treatment. In the present work, a proteomic strategy was used to characterize the intracellular signaling pathways and the molecular targets downstream of STEAP1 in PCa cells. A label-free approach was applied using an Orbitrap LC-MS/MS system to characterize the proteome of STEAP1-knockdown PCa cells. More than 6700 proteins were identified, of which a total of 526 proteins were found differentially expressed in scramble siRNA versus STEAP1 siRNA (234 proteins up-regulated and 292 proteins down-regulated). Bioinformatics analysis allowed us to explore the mechanism through which STEAP1 exerts influence on PCa, revealing that endocytosis, RNA transport, apoptosis, aminoacyl-tRNA biosynthesis, and metabolic pathways are the main biological processes where STEAP1 is involved. By immunoblotting, it was confirmed that STEAP1 silencing induced the up-regulation of cathepsin B, intersectin-1, and syntaxin 4, and the down-regulation of HRas, PIK3C2A, and DIS3. These findings suggested that blocking STEAP1 might be a suitable strategy to activate apoptosis and endocytosis, and diminish cellular metabolism and intercellular communication, leading to inhibition of PCa progression.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Claudio Jorge Maia reports financial support and equipment, drugs, or supplies were provided by University of Beira Interior. Claudio J Maia reports a relationship with University of Beira Interior that includes: employment.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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