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

, are resistant to chemotherapy, and are often fatal.

To carry out the current study, first author Liling Wan, who earned her doctorate from Princeton this year, conducted experiments on mice that were genetically modified to lack the MTDH gene. "We observed normal development and growth in mice that lacked the MTDH gene, and therefore determined that the gene is non-essential for normal life," Wan said.

Wan and colleagues then looked at mice that were genetically engineered to develop breast cancer and found that the mice without MTDH had significantly fewer tumors and as little as a tenth of the tumor burden observed in mice with the gene.

Further experiments revealed that only when MTDH is bound to its partner protein, SND1, does the tumor-initiating and metastatic behavior ensue. Under stress conditions during the formation of tumors, MTDH protects SND1 from degradation. This allows tumor-initiating cells, the root of tumors, to survive and expand, eventually giving rise to large tumors. When MTDH was genetically deleted, SND1 became unstable under oncogenic stress and was no longer able to support tumor initiation. These cells underwent stress-induced cell death and lost the ability to initiate tumors. Thus, when Wan knocked out either the MTDH gene or the SND1 gene, tumors did not form or were very small.

The team also looked at MTDH and SND1 in samples of human breast tumors supplied by collaborators at the Rutgers Cancer Institute of New Jersey (Rutgers-CINJ) led by Bruce Haffty, professor and chair of radiation oncology at Rutgers-CINJ, Robert Wood Medical School and New Jersey Medical School. The team observed a strong correlation of MTDH and SND1 expression in human tumors, indicating significant clinical relevance of this molecular partnership.

"Our goal is to someday have a drug that could improve, cure or control breast cancer by targeting the particular pathways that are associated with metastasis and the
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Contact: Catherine Zandonella
czandone@princeton.edu
609-258-0541
Princeton University
Source:Eurekalert  

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