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CSHL scientists show how a protein that determines cell polarity prevents breast cancer
Date:11/26/2008

i.e., present in abnormal quantity, in human breast cancer. Myc is known to activate pathways of both growth and death in breast epithelial cells. In fact, the only way that cancer can occur when Myc is overexpressed is if some other mechanism blocks its propensity to induce abnormal cells to commit suicide, a process called apoptosis. Muthuswamy and colleagues now identify this "other mechanism" as the loss of the Scribble protein, which thus is revealed to be a tumor suppressor protein.

Cells engineered by the CSHL team to lack Scribble and overexpress Myc not only stayed alive, but also went into a growth overdrive. The combined effect of polarity loss and Myc overactivation was the formation of unusually large and fast-growing breast epithelial tumors.

The CSHL team worked out the molecular players and specific intracellular pathway controlled by Scribble to initiate cell death. This revealed that Scribble only works as a cancer deflector when it finds itself in the right location--within the junctions between cells. Cellular disorientation occurs when mutations in the gene that orders Scribble to be produced in a cell either prevents its expression or causes it to be expressed in the wrong location within the cell. In either case, the same severe consequence ensues: cancer progression.

How Scribble gets deregulated in cancer remains a mystery. The CSHL team is now addressing the question of how the deregulated Scribble pathway can be targeted for diagnosis and treatment.


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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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