title: Scribble acts as an oncogene in Eμ-myc-driven lymphoma.
abstract: Scribble complex proteins maintain apicobasal polarity, regulate cell fate determination and function as tumour suppressors in epithelial tissue. Despite evidence that the function of Scribble is maintained in the lymphocyte lineage, we still understand little about its role as a tumour suppressor in haematological malignancies. Using the Eμ-myc model of Burkitt's lymphoma we investigated the role of Scribble in lymphomagenesis. We found that contrary to its well-documented tumour suppressor role in epithelial tissue, loss of Scribble expression delayed the expansion of peripheral B cells and delayed the onset of Eμ-myc-driven lymphoma. This was despite upregulated ERK phosphorylation levels in Scribble-deficient tumours, which are associated with loss of Scribble expression and the development of more aggressive Burkitt's lymphoma. Interestingly, the developmental stage of lymphoma was unaffected by Scribble expression challenging any role for Scribble in fate determination in the haematopoetic lineage. These data provide evidence for oncogenic properties of Scribble in Myc-driven B-cell lymphomagenesis, reinforcing recent findings that overexpression of a mutant form of Scribble can act as an oncogene in epithelial cells. Our results support the growing appreciation that the tumour regulatory functions of Scribble, and other polarity protein family members, are context dependent.
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: E D
authors.initials: ED
authors.lastname: Hawkins
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Oliaro
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: K M
authors.initials: KM
authors.lastname: Ramsbottom
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.|Cancer Therapeutics Programs, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Newbold
authors.affiliation: Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.|Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.|Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.|Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Victoria, Australia.|Cell cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: P O
authors.initials: PO
authors.lastname: Humbert
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.|Cancer Therapeutics Programs, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: R W
authors.initials: RW
authors.lastname: Johnstone
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.|Centre for Micro-Photonics, Swinburne University of Technology, Hawthorn, Victoria, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Russell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009857:Oncogenes; D015533:Transcriptional Activation / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins