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Transcription Factor Found to Be Master Regulator in Cancer Metastasis

By BiotechDaily International staff writers
Posted on 20 Jun 2013
Image: Mammary epithelial cells that have undergone an epithelial-mesenchymal transition (EMT) exhibit a change in cell morphology with actin stress fibers (red) and with focused cell adhesion points (green) (Photo courtesy of Dr. Nathalie Meyer-Schaller, University of Basel).
Image: Mammary epithelial cells that have undergone an epithelial-mesenchymal transition (EMT) exhibit a change in cell morphology with actin stress fibers (red) and with focused cell adhesion points (green) (Photo courtesy of Dr. Nathalie Meyer-Schaller, University of Basel).
Image: In mammary epithelial cells in which the Sox4 transcription factor is missing this change is not apparent, and cancer cells cannot metastasize (Photo courtesy of Dr. Nathalie Meyer-Schaller, University of Basel).
Image: In mammary epithelial cells in which the Sox4 transcription factor is missing this change is not apparent, and cancer cells cannot metastasize (Photo courtesy of Dr. Nathalie Meyer-Schaller, University of Basel).
In the process of metastasis, the movement of cancer cells to diverse regions of the body, a specific master regulator gene plays a key role: a transcription factor called Sox4 triggers a sequence of genes and triggers the process. Sox4 suppression and subsequent processes may, according to Swiss researchers, prevent metastasis in cancer patients.

This new discovery was made by scientists from the University of Basel (Switzerland) and the Friedrich Miescher Institute for Biomedical Research (Basel, Switzerland). Their findings were published June 10, 2013, in the journal Cancer Cell.

The leading cause of death in cancer patients is metastasis, the formation of secondary tumors in other organs such as the lung, brain, and liver. Cancer cells detach from the original primary tumor and reach one cell or group of cells in another organ. The cells of the body typically stay in place by adhering to an extracellular material. However, cancer cells learn how to release themselves from these bonds and invade surrounding tissues, blood, and the lymphatic system.

The transformation of specialized, sedentary cells into drifting, invasive, and unspecialized cells is called epithelial-mesenchymal transition (EMT), which is essential for metastasis to occur. EMT is a multistage process, which is accompanied by a fundamental change in cell morphology and number of genetic programs. The molecular processes that control EMT, however, are still not well understood.

The research groups of Prof. Gerhard Christofori of the department of biomedicine at the University of Basel; Prof. Erik van Nimwegen from the Biozentrum, University of Basel; and Prof. Dirk Schuebeler from the Friedrich Miescher Institute have discovered a master regulator of metastasis and EMT: the transcription factor Sox4 is upregulated in its activity and triggers the expression of a number of genes that play an important role during EMT and metastasis.

Sox4 specifically encourages the expression of the enzyme Ezh2, a methyltransferase, which generally influences methylation of specific proteins (histones), the packaging of the genetic material, and thus its readability and gene expression. Because of this change in genetic information, the behavior and function of cells are reprogrammed—a mechanism that is observed during metastasis. Such an alteration in gene expression is also found in patients with malignant cancer and metastasis and correlates with a poor prognosis.

This new research points to the prospect that the suppression of the transcription factor Sox4 and especially the methyltransferase Ezh2 could inhibit metastasis in cancer patients. Appropriate pharmaceuticals are currently being developed but they still need to undergo clinical trials before being used in patients.

Related Links:
University of Basel
Friedrich Miescher Institute for Biomedical Research


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