Here's why 'Jekyll and Hyde' protein prevents as well as spreads cancer

A new research has explained why a protein that suppresses tumors also causes metastasis.

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, raising 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 and one example is a protein, transforming growth factor beta (TGF-Beta) that suppresses tumor progression in pre-malignant cells, can also lead to the spread of cancer.

It has been a long-time puzzle how and when TGF-Beta switches its functional roles from a tumor suppressor to a metastasis promoter and now, scientists at The University of Texas believe they have an answer.

The research demonstrates that another protein, known as 14-3-3 zeta, can switch TGF-Beta from suppressing tumors in pre-cancerous cells to promoting metastasis in breast cancer cells, spreading to the bones by changing the TGF-Beta's partner proteins.

Dihua Yu said that TGF-Beta has a dual role as both a tumor suppressor in normal and pre-malignant cells, and a metastasis promoter in late-stage cancer and the molecular mechanism by which TGF-Beta switches its role has long been an unsolved mystery for cancer researchers.

Yu added that TGF-Beta's known critical role in cancer has led to numerous efforts developing TGF-Beta 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-Beta therapies and they have developed a model that proposes that TGF-Beta's complicated nature may be governed by the cellular effects of SMAD's partner proteins.

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

The results are published in Cancer Cell.