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Scribble acts as an oncogene in Eμ-myc-driven lymphoma
E D Hawkins1,2, J Oliaro1,2, K M Ramsbottom1,2
1Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Oncogene
|May 19, 2015
Summary
Loss of Scribble protein, typically a tumor suppressor, unexpectedly delayed lymphoma onset in a mouse model. This suggests Scribble may promote certain cancers, highlighting context-dependent protein function in disease.
Area of Science:
- Cell biology
- Cancer research
- Immunology
Background:
- Scribble complex proteins are crucial for apicobasal polarity, cell fate, and tumor suppression in epithelial tissues.
- While Scribble's function is preserved in lymphocytes, its role in hematological malignancies remains largely unknown.
- Investigating Scribble's function in lymphomagenesis is essential for understanding its broader role in cancer.
Purpose of the Study:
- To investigate the role of Scribble complex in lymphomagenesis using the Eμ-myc mouse model of Burkitt's lymphoma.
- To determine if Scribble acts as a tumor suppressor or oncogene in B-cell lymphomas.
- To explore the impact of Scribble expression on lymphoma development and progression.
Main Methods:
- Utilized the Eμ-myc mouse model to study Burkitt's lymphoma.
- Assessed the impact of Scribble loss of expression on peripheral B cell expansion and lymphoma onset.
- Analyzed ERK phosphorylation levels in Scribble-deficient tumors.
Main Results:
- Loss of Scribble expression delayed peripheral B cell expansion and the onset of Eμ-myc-driven lymphoma.
- Scribble-deficient tumors exhibited upregulated ERK phosphorylation, a marker associated with aggressive Burkitt's lymphoma.
- Scribble expression did not affect the developmental stage of lymphoma, challenging its role in hematopoietic cell fate determination.
Conclusions:
- Scribble complex exhibits oncogenic properties in Myc-driven B-cell lymphomagenesis, contrary to its tumor suppressor role in epithelial tissues.
- These findings support the context-dependent nature of Scribble's tumor regulatory functions.
- The study underscores the need to consider the specific cellular environment when evaluating the role of polarity proteins in cancer.
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