Scribble acts as an oncogene in Emu-myc-driven lymphoma

Hawkins, ED; Oliaro, J; Ramsbottom, KM; Newbold, A; Humbert, PO; Johnstone, RW; Russell, SM

Author(s): Hawkins, ED; Oliaro, J; Ramsbottom, KM; Newbold, A; Humbert, PO; Johnstone, RW; Russell, SM;
Details: Publication Year 2016-03-03,Volume 35,Issue #9,Page 1193-7
Journal Title: Oncogene
Publication Type: Journal Article
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 Emu-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 Emu-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.
Publisher: Springer Nature
Keywords: Animals; Apoptosis/genetics; B-Lymphocytes/metabolism/pathology; Burkitt Lymphoma/*genetics/pathology; Cell Line, Tumor; Humans; Lymphoma, B-Cell/*genetics/pathology; Membrane Proteins/*biosynthesis/genetics; *Oncogenes; Transcriptional Activation/genetics; Tumor Suppressor Proteins/*biosynthesis/genetics
Research Division(s): Immunology
PubMed ID: 25982280
Publisher's Version: https://doi.org/10.1038/onc.2015.167
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-05-26 02:39:19

Last Modified: 2017-05-26 02:55:03