News Release

Pathway transforms normal cells into aggressive tumors

Characteristics applicable to cancers; development could lead to better diagnostics

Peer-Reviewed Publication

Lerner Research Institute

Monday, February 21, 2011 – Cleveland – A biological pathway that transforms normal cells into aggressive tumors has been discovered by researchers at Cleveland Clinic's Lerner Research Institute.

This research, led by Philip Howe, Ph.D., of the Cancer Biology Department of the Lerner Research Institute of Cleveland Clinic, was recently published in a recent issue of Molecular Cell.

This research helps define the cellular events that lead to metastasis. While the study used breast cells, the pathway offers characteristics that are applicable to cancers in general. It is hoped that this improved understanding of cancer development will lead to better diagnostic, preventative, and therapeutic procedures for the disease.

These studies build on those published by the same group last year in Nature Cell Biology, which identified the components of a molecular complex that prevents the processing of genetic material necessary for tumor development – and a protein that reverses this to permit tumor-forming ability.

The current publication further defines this mechanism by showing evidence in a mouse model that tumor progression hinges on the role of a specific molecular factor called "hnRNP E1." Mice lacking hnRNP E1 developed metastatic tumors when challenged with normal, non-invasive breast cells: mice with hnRNP E1 did not.

The genetic material whose expression is regulated by this mechanism is necessary for what is known as the epithelial-mesenchymal transition (EMT). EMT describes how cells that are normally stationary become mobile. This process is essential for embryonic development. Once development is complete, the process is silenced – except when a tumor forms. That is when the "safety" (i.e. hnRNP E1) is removed from the EMT-blocking complex, and the ensuing cell mobility promotes tumor progression.

Since EMT is not necessary in the normal adult, identifying the status of hnRNP E1 may be useful as a diagnostic approach for cancer. Furthermore, a strategy that prevents removing it from the complex may make it possible to specifically target cancerous versus normal tissue.

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About Cleveland Clinic

Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. It was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. About 2,100 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. In addition to its main campus, Cleveland Clinic operates nine regional hospitals and 15 Family Health Centers in Northeast Ohio, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and opening in 2012, Cleveland Clinic Abu Dhabi. In 2009, there were more than 4.6 million visits throughout the Cleveland Clinic health system and 170,000 hospital admissions. Patients came for treatment from every state and from more than 100 countries. Visit us at www.clevelandclinic.org.


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