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Scottish author Robert Louis Stevenson tapped into primal fears when he penned ¡°Dr. Jekyll and Mr. Hyde,¡± a 19th-century novel about a sinister physician that raised the question, ¡°Can evil and good exist in the same person?¡±

As it turns out, cancer researchers are discovering that ¡°good vs. bad¡± can also exist in the world of molecular genetics. One example is a protein ¡ª transforming growth factor beta (TGF-?_) ¡ª that suppresses tumor progression in pre-malignant cells, but can also lead to the spread of cancer. It has been a long-time puzzle how and when TGF-?_ switches its functional roles from a tumor suppressor to a metastasis promoter. Now, scientists at MD Anderson believe they have an answer.

A study led by , deputy chair of Molecular and Cellular Oncology, demonstrates that another protein, known as 14-3-3 zeta, can switch TGF-?_ from suppressing tumors in pre-cancerous cells to promoting metastasis in breast cancer cells ¨C spreading to the bones by changing the TGF-?_¡¯s partner proteins.

Yu¡¯s results are published in this month¡¯s issue of .

¡°TGF-?_ has a dual role as both a tumor suppressor in normal and pre-malignant cells, and a metastasis promoter in late-stage cancer,¡± said Yu, who also serves as the Hubert L. & Olive Stringer Distinguished Chair in Basic Science. ¡°The molecular mechanism by which TGF-?_ switches its role has long been an unsolved mystery for cancer researchers.¡±

Yu and her team may have provided a key to solving that mystery in part by explaining how 14-3-3 zeta destabilizes a key protein, p53, subsequently switching off TGF-?_¡¯s ability to suppress tumors. In addition, it also promotes the spread of cancer to bones by stabilizing another protein, GLi2.

¡°TGF-?_¡¯s known critical role in cancer has led to numerous efforts developing TGF-?_ inhibitors for anti-cancer therapeutics, but its penchant for both suppressing tumor progression while serving as a springboard for cancer metastasis has been a major obstacle in the development of anti-TGF-?_ therapies,¡± said Yu. ¡°We have developed a model that proposes that TGF-?_¡¯s complicated nature may be governed by the cellular effects of SMAD¡¯s partner proteins.¡±

SMAD proteins help to regulate the activity of particular genes, as well as cell growth and division. They, in essence, transmit TGF-?_ signals from outside the cell to the nucleus, impacting how the cell produces other proteins. SMAD adds to TGF-?_¡¯s Jekyll and Hyde nature by partnering with p53 to suppress tumors in pre-malignant cells, while helping the protein GLi2 to promote the cancer¡¯s spread to bones.

Better definition of this molecular mixing bowl of proteins may lead to new therapies that target TGF-?_¡¯s critical role in cancer in more effective ways.

¡°Because TGF-?_ plays important roles in various physiological functions, it is crucial that we look at how to develop more specific drugs that selectively target TGF-?_ in cancer so as to discourage its ability to cause metastasis while maintaining its tumor suppression abilities in pre-cancerous cells,¡± said Yu.