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GD2 and its biosynthetic enzyme GD3 synthase promote tumorigenesis in prostate cancer by regulating cancer stem cell behavior.
Bhat, Aaqib M; Mohapatra, Bhopal C; Luan, Haitao; Mushtaq, Insha; Chakraborty, Sukanya; Kumar, Siddhartha; Wu, Wangbin; Nolan, Ben; Dutta, Samikshan; Storck, Matthew D; Schott, Micah; Meza, Jane L; Lele, Subodh M; Lin, Ming-Fong; Cook, Leah M; Corey, Eva; Morrissey, Colm; Coulter, Donald W; Rowley, M Jordan; Natarajan, Amarnath; Datta, Kaustubh; Band, Vimla; Band, Hamid.
Afiliación
  • Bhat AM; Eppley Institute for Research in Cancer and Allied Diseases, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.
  • Mohapatra BC; Department of Genetics, Cell Biology and Anatomy, College of Medicine, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
  • Luan H; Department of Genetics, Cell Biology and Anatomy, College of Medicine, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA. bmohapat@unmc.edu.
  • Mushtaq I; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. bmohapat@unmc.edu.
  • Chakraborty S; Eppley Institute for Research in Cancer and Allied Diseases, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.
  • Kumar S; Eppley Institute for Research in Cancer and Allied Diseases, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.
  • Wu W; Departments of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
  • Nolan B; Incyte Corporation, Wilmington, DE, USA.
  • Dutta S; Eppley Institute for Research in Cancer and Allied Diseases, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.
  • Storck MD; Department of Genetics, Cell Biology and Anatomy, College of Medicine, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
  • Schott M; Eppley Institute for Research in Cancer and Allied Diseases, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.
  • Meza JL; Eppley Institute for Research in Cancer and Allied Diseases, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.
  • Lele SM; Department of Genetics, Cell Biology and Anatomy, College of Medicine, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
  • Lin MF; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Cook LM; Eppley Institute for Research in Cancer and Allied Diseases, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.
  • Corey E; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Morrissey C; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
  • Coulter DW; Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA.
  • Rowley MJ; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
  • Natarajan A; Departments of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
  • Datta K; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
  • Band V; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Band H; Departments of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Sci Rep ; 14(1): 13523, 2024 06 12.
Article en En | MEDLINE | ID: mdl-38866755
ABSTRACT
While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Identification of novel targetable pathways that contribute to tumor progression in PC could open new therapeutic options. The di-ganglioside GD2 is a target of FDA-approved antibody therapies in neuroblastoma, but the role of GD2 in PC is unexplored. Here, we show that GD2 is expressed in a small subpopulation of PC cells in a subset of patients and a higher proportion of metastatic tumors. Variable levels of cell surface GD2 expression were seen on many PC cell lines, and the expression was highly upregulated by experimental induction of lineage progression or enzalutamide resistance in CRPC cell models. GD2high cell fraction was enriched upon growth of PC cells as tumorspheres and GD2high fraction was enriched in tumorsphere-forming ability. CRISPR-Cas9 knockout (KO) of the rate-limiting GD2 biosynthetic enzyme GD3 Synthase (GD3S) in GD2high CRPC cell models markedly impaired the in vitro oncogenic traits and growth as bone-implanted xenograft tumors and reduced the cancer stem cell and epithelial-mesenchymal transition marker expression. Our results support the potential role of GD3S and its product GD2 in promoting PC tumorigenesis by maintaining cancer stem cells and suggest the potential for GD2 targeting in advanced PC.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Sialiltransferasas / Células Madre Neoplásicas / Carcinogénesis / Gangliósidos Límite: Animals / Humans / Male Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Sialiltransferasas / Células Madre Neoplásicas / Carcinogénesis / Gangliósidos Límite: Animals / Humans / Male Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos