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Proteomic Signatures of Cellular Reprogramming in Bladder Cancer: Insights into the Acquisition of Cancer Stem-like States and Phenotypic Plasticity.

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Title: Proteomic Signatures of Cellular Reprogramming in Bladder Cancer: Insights into the Acquisition of Cancer Stem-like States and Phenotypic Plasticity.
Authors: Barlak BSR; Protein Research and Proteomics Laboratory, Department of Medical Biology, Faculty of Medicine, Kocaeli University, Izmit, Türkiye., Iskender B; Protein Research and Proteomics Laboratory, Department of Medical Biology, Faculty of Medicine, Kocaeli University, Izmit, Türkiye banu.iskender@kocaeli.edu.tr.
Source: Cancer genomics & proteomics [Cancer Genomics Proteomics] 2026 Mar-Apr; Vol. 23 (2), pp. 300-321.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: International Institute of Anticancer Research Country of Publication: Greece NLM ID: 101188791 Publication Model: Print Cited Medium: Internet ISSN: 1790-6245 (Electronic) Linking ISSN: 11096535 NLM ISO Abbreviation: Cancer Genomics Proteomics Subsets: MEDLINE
Imprint Name(s): Original Publication: Kapandriti, Attiki, Greece : International Institute of Anticancer Research, [2004]-
MeSH Terms: Urinary Bladder Neoplasms*/pathology , Urinary Bladder Neoplasms*/metabolism , Urinary Bladder Neoplasms*/genetics , Neoplastic Stem Cells*/metabolism , Neoplastic Stem Cells*/pathology , Proteomics*/methods , Cellular Reprogramming*, Humans ; Cell Line, Tumor ; Phenotype ; Epithelial-Mesenchymal Transition ; Cell Plasticity
Abstract: Background/aim: Reprogramming somatic cells to an embryonic state opens a transformative pathway to convert cancer cells into benign ones. By delving into the changes that occur during this process, we can enhance our understanding of tumor development and unlock groundbreaking therapeutic strategies. In this study, we successfully reprogrammed the bladder cancer cell line using Yamanaka factors and conducted a stage-specific, comprehensive proteomic analysis of the resulting molecular changes.
Materials and Methods: The bladder cancer cell line HTB-4 was reprogrammed and cultured on vitronectin-coated surfaces following Sendai virus reprogramming, enabling a thorough evaluation of pluripotent marker expression. Both parental and reprogrammed cells were tested for proliferation, migration, invasion, and colony formation. nLC-MS/MS analysis was performed to identify molecular differences between parental bladder cancer cells and reprogrammed cells across initial passages.
Results: Reprogrammed HTB-4 cells retain their ability to adhere and exhibit significant expression of pluripotency-associated proteins, forming colony-like structures. Stage-specific proteomic analyses reveal notable differences between reprogrammed cells and progenitor cells, particularly in pathways related to epithelial-mesenchymal transition, stem cell maintenance, and differentiation.
Conclusion: We developed an in vitro model of bladder cancer reprogramming that identifies biomarkers associated with the induction of stem-like states and cellular plasticity. Our findings reveal significant stage-specific proteomic changes offering insights into the hierarchical organization of bladder cancer and the molecular mechanisms underlying the cancer stem cell phenotype. These results facilitate the development of more precise, patient-specific in vitro models for studying tumor recurrence and treatment resistance. However, further mechanistic studies are needed to translate effectively potential biomarkers into clinical practice.
(Copyright © 2026, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
References: Nat Commun. 2020 Jan 17;11(1):361. (PMID: 31953406)
Mater Sci Eng C Mater Biol Appl. 2018 Dec 1;93:157-169. (PMID: 30274048)
Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230)
Annu Rev Cancer Biol. 2018 Mar;2:271-289. (PMID: 29756093)
EMBO Rep. 2014 Mar;15(3):244-53. (PMID: 24531722)
Mol Cancer. 2023 Nov 28;22(1):189. (PMID: 38017433)
Cell Rep. 2012 Dec 27;2(6):1579-92. (PMID: 23260666)
Mol Syst Biol. 2011 Nov 22;7:550. (PMID: 22108792)
Trends Genet. 2016 Jan;32(1):29-41. (PMID: 26675384)
Cancer Diagn Progn. 2024 Nov 3;4(6):783-788. (PMID: 39502620)
EMBO J. 2011 May 4;30(9):1778-89. (PMID: 21468033)
Nat Rev Genet. 2016 May;17(5):284-99. (PMID: 26972587)
Stem Cell Res Ther. 2022 Sep 5;13(1):459. (PMID: 36064437)
Signal Transduct Target Ther. 2024 May 20;9(1):132. (PMID: 38763973)
Essays Biochem. 2022 Sep 16;66(4):413-422. (PMID: 35611837)
Cancer Genomics Proteomics. 2012 Sep-Oct;9(5):275-86. (PMID: 22990107)
Stem Cell Res. 2020 Dec;49:102062. (PMID: 33202305)
Cell Rep. 2022 Apr 26;39(4):110721. (PMID: 35476996)
J Biomed Sci. 2018 Jul 19;25(1):57. (PMID: 30025541)
Trends Cancer. 2016 Sep;2(9):485-494. (PMID: 27722205)
Semin Cell Dev Biol. 2014 Jun;30:174-80. (PMID: 24641889)
Stem Cells Int. 2019 Nov 18;2019:8036035. (PMID: 31827534)
J Biol Chem. 2016 Jan 8;291(2):752-61. (PMID: 26598518)
FEBS J. 2017 Feb;284(3):391-398. (PMID: 27398614)
Cancer Genomics Proteomics. 2009 Jan-Feb;6(1):19-29. (PMID: 19451087)
Br J Cancer. 2020 Jan;122(2):182-193. (PMID: 31819175)
J Proteomics. 2013 Jun 28;86:70-84. (PMID: 23615220)
Nat Med. 2016 Dec 6;22(12):1392-1401. (PMID: 27923030)
Cancer Commun (Lond). 2019 Aug 29;39(1):48. (PMID: 31464654)
Cell Regen. 2020 Nov 12;9(1):22. (PMID: 33179756)
Cancer Res. 2020 Oct 1;80(19):4037-4041. (PMID: 32554552)
Nat Rev Mol Cell Biol. 2021 Oct;22(10):671-690. (PMID: 34272502)
Stem Cells Int. 2020 Jul 6;2020:8863539. (PMID: 32695182)
J Lipid Res. 2010 Aug;51(8):2082-9. (PMID: 20110442)
Nat Commun. 2014 Dec 10;5:5613. (PMID: 25494451)
Cancer Genomics Proteomics. 2024 Jul-Aug;21(4):388-394. (PMID: 38944424)
Cell Rep Med. 2025 Aug 19;6(8):102255. (PMID: 40749681)
Stem Cells. 2016 Apr;34(4):832-46. (PMID: 26753613)
Cancer Discov. 2022 Jan;12(1):31-46. (PMID: 35022204)
Tumour Biol. 2016 Oct;37(10):13237-13245. (PMID: 27456363)
EMBO J. 2015 Mar 12;34(6):739-47. (PMID: 25712212)
Stem Cells. 2008 Sep;26(9):2257-65. (PMID: 18599809)
Cell. 2010 Nov 12;143(4):508-25. (PMID: 21074044)
Cell. 2016 Jun 30;166(1):21-45. (PMID: 27368099)
Contributed Indexing: Keywords: Bladder cancer; Yamanaka factors; cellular plasticity; proteomics; reprogramming
Entry Date(s): Date Created: 20260302 Date Completed: 20260710 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC12951382
DOI: 10.21873/cgp.20578
PMID: 41771576
Database: MEDLINE
Description
ISSN:1790-6245
DOI:10.21873/cgp.20578