CD133 + brain tumor-initiating cells are dependent on STAT3 signaling to drive medulloblastoma recurrence.

Autor: Garg N; McMaster Stem Cell and Cancer Research Institute, Hamilton, Ontario, Canada.; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada., Bakhshinyan D; McMaster Stem Cell and Cancer Research Institute, Hamilton, Ontario, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada., Venugopal C; McMaster Stem Cell and Cancer Research Institute, Hamilton, Ontario, Canada.; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada., Mahendram S; McMaster Stem Cell and Cancer Research Institute, Hamilton, Ontario, Canada.; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada., Rosa DA; Department of Chemistry, University of Toronto, Mississauga, Ontario, Canada., Vijayakumar T; McMaster Stem Cell and Cancer Research Institute, Hamilton, Ontario, Canada.; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada., Manoranjan B; McMaster Stem Cell and Cancer Research Institute, Hamilton, Ontario, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.; Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada., Hallett R; McMaster Centre for Functional Genomics, McMaster University, Hamilton, Ontario, Canada., McFarlane N; McMaster Stem Cell and Cancer Research Institute, Hamilton, Ontario, Canada.; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada., Delaney KH; Departement of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada., Kwiecien JM; Departement of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.; Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, Lublin, Poland., Arpin CC; Department of Chemistry, University of Toronto, Mississauga, Ontario, Canada., Lai PS; Department of Chemistry, University of Toronto, Mississauga, Ontario, Canada., Gómez-Biagi RF; Department of Chemistry, University of Toronto, Mississauga, Ontario, Canada., Ali AM; Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt., de Araujo ED; Department of Chemistry, University of Toronto, Mississauga, Ontario, Canada., Ajani OA; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada., Hassell JA; McMaster Stem Cell and Cancer Research Institute, Hamilton, Ontario, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.; McMaster Centre for Functional Genomics, McMaster University, Hamilton, Ontario, Canada.; Departments of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada., Gunning PT; Department of Chemistry, University of Toronto, Mississauga, Ontario, Canada., Singh SK; McMaster Stem Cell and Cancer Research Institute, Hamilton, Ontario, Canada.; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.; Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2017 Feb 02; Vol. 36 (5), pp. 606-617. Date of Electronic Publication: 2016 Oct 24.
DOI: 10.1038/onc.2016.235
Abstrakt: Medulloblastoma (MB), the most common malignant paediatric brain tumor, is currently treated using a combination of surgery, craniospinal radiotherapy and chemotherapy. Owing to MB stem cells (MBSCs), a subset of MB patients remains untreatable despite standard therapy. CD133 is used to identify MBSCs although its functional role in tumorigenesis has yet to be determined. In this work, we showed enrichment of CD133 in Group 3 MB is associated with increased rate of metastasis and poor clinical outcome. The signal transducers and activators of transcription-3 (STAT3) pathway are selectively activated in CD133 + MBSCs and promote tumorigenesis through regulation of c-MYC, a key genetic driver of Group 3 MB. We screened compound libraries for STAT3 inhibitors and treatment with the selected STAT3 inhibitors resulted in tumor size reduction in vivo. We propose that inhibition of STAT3 signaling in MBSCs may represent a potential therapeutic strategy to treat patients with recurrent MB.
Databáze: MEDLINE
Externí odkaz: