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Overexpressed protein converts noninvasive breast cancer into invasive disease
Date:9/8/2009

HOUSTON ― Active, but non-invasive breast cancer is set free to roam as invasive breast cancer when an overexpressed protein converts it to a different cell type, scientists at The University of Texas M. D. Anderson Cancer Center report in the Sept. 9 issue of the journal Cancer Cell.

"We have discovered a key molecular mechanism for the deadly transition of non-invasive breast cancer into invasive disease," said senior author Dihua Yu, M.D., Ph.D., professor in M. D. Anderson's Department of Molecular and Cellular Oncology.

Overexpression of the protein 14-3-3ζ (zeta) launches a molecular cascade that removes bonds that tie the premalignant cells together and hold them in place, converting them from stationary epithelial cells to highly mobile mesenchymal-like cells, Yu and colleagues report. This epithelial-to-mesenchymal transition (EMT) is recognized as a crucial step in metastasis, the spread of cancer to distant organs that causes 90 percent of all cancer deaths.

The researchers show that 14-3-3ζ teams with the oncoprotein ErbB2, also known as HER2, in a two-hit process to convert normal mammary cells to invasive cancer cells.

In addition to identifying this key step in EMT, Yu notes the findings also provide:

  • A biomarker in 14-3-3ζ to identify high-risk patients for more aggressive treatment before their noninvasive breast cancer converts to invasive disease.

  • New therapeutic targets among the components of the molecular pathway launched by 14-3-3ζ. Some drugs already aim at these targets, Yu said.

  • A solution to a puzzling mystery about how a subset of non-invasive breast cancer with excessive presence of a ErbB2/HER2 develops into invasive breast cancer.

Yu and colleagues previously showed that 14-3-3ζ is overexpressed in many other cancer types, like lung, liver, uterine, stomach cancers. "Our findings might hav
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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