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Diabolical duo: Known breast cancer gene needs a partner to initiate and spread tumors
Date:6/26/2014

progression of disease," Haffty said. "Although these results are too early to have an immediate impact on cancer treatment, they are very exciting."

Eileen White, associate director of basic science at Rutgers-CINJ, who is familiar with the work but did not directly participate in it, said, "This research found that the proteins MTDH and SND1 were highly expressed in a battery of different breast cancers, so interfering with these two proteins might have anti-cancer activity in a spectrum of breast cancers."

To learn more about the physical nature of the interaction of MTDH with SND1 and to find a way to block this cancer-promoting interaction, the Kang lab enlisted the help of researchers led by Yongna Xing at the University of Wisconsin-Madison. The team used X-ray crystallography a technique that enables researchers to see structures that are too small to see with microscopes to visualize the two proteins when bound to each other.

The researchers found that MTDH has two finger-like projections that stick into two pockets on the surface of SND1. "They are like two fingers sticking into the holes of a bowling ball," said Kang. The discovery of the binding gave rise to ideas about how to block it and thus block tumor initiation.

The team is currently screening small molecules that could block the binding of MTDH to SND1 and curtail its tumor-promoting functions. "MTDH stabilizes SND1 and that is the lifeboat for the so-called cancer stem cells that initiate primary tumors and metastasis," Kang said. "Without MTDH, SND1 will be degraded and the seeds of cancer will be wiped out."

Additional research from the Kang lab and other researchers around the world has revealed that Metadherin gene overexpression is seen in about 20 cancer types, indicating that an MTDH-blocking strategy may be able to overcome a variety of cancers.


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Contact: Catherine Zandonella
czandone@princeton.edu
609-258-0541
Princeton University
Source:Eurekalert  

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