New Approaches in Studying Cancer: The Scribble Protein

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Why does cancer develop? The answer is more complicated than most people realize. At the most basic level, all cancers develop as a result of cell division gone wild: an uncontrollable deviation in the cell cycle which results in one mutant cell divides continuously, ignoring the normal boundaries of the cycle of cell division and death.

As these abnormal cells continue dividing they pile up, one on top of the other, forming a tumor. These cells have no restraints on number, age, and location: while most cells are stationary, staying exactly where they are supposed to be, malignant cells can spread across the boundaries of tissues and organs, and even enter the bloodstream.

But what causes this abnormal development? As demonstrated by recent developments in the study of breast cancer, the question of how cancers develop is far more complicated than abnormal, unrestrained cell division.

A New Player in the Development of Breast Cancer

In normal healthy breast tissue, the cells which line breast ducts have a characteristic shape. This shape is necessary to retain the structure and function of a healthy breast. All breast cancers, regardless of the type of genetic mutation that might be involved, involve the loss of this characteristic organization of tissue – but virtually nothing is known about how and why this occur when tissue becomes cancerous.

Recently, however, some light has been shed on this problem. A group of scientists have discovered that a protein known as “scribble,” previously known as a regulator of cell shape in worms and fruit flies, is also involved in the development of breast cancer.

Normally, the scribble protein allows breast epithelial cells to form duct-like structures, and also to resist the development of malignancy. If scribble stops functioning normally, these cells lose their characteristic shape, and also lose their ability to resist becoming malignant.

3D Cell Cultures

An important feature of this work was that the cells used were grown in an experimental system which allowed cells to grow in three dimensions, mimicking what would be found in a real breast: in this model system, healthy cells were able to form structures similar to those formed in normal breast tissue.

In these cells, the scribble protein lines the sides of the cells, aiding in the development of cell polarity, and providing cells with “instructions” on the required orientation. When allowed to grow in three dimensions, the cells form a structure similar to a hollow ball.

When the scribble protein is missing or non-functional, however, cells in this model system undergo radical changes in growth and behavior. The cells no longer oriented themselves, and instead began to pile up on one another, filling the center of the hollow “ball.”

A New Tumor-Suppressor Protein

Most tumor suppressors are genes which have been shown to be over-expressed in tumor cells. In the case of scribble, however, the opposite is true: cancerous growths can develop in the absence of this protein. In situations where scribble is either not produced, or is expressed in the wrong location in a cell, the development of tumors is a certainty. While this new information designates scribble as a potential new target for breast cancer diagnostic tests and even new treatments, the question of how scribble function becomes abnormal remains unanswered.

References

Zhan L, Rosenberg A, Bergami KC, Yu M, Xuan Z, Jaffe AB, Allred C, Muthuswamy SK. Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell. 2008 Nov 28;135(5):865-78.