Posted by: Dan | December 11, 2006

Spemann Organizer Gene Promotion of Metastasis

One popular area of research in cell migration in vivo is the role of homeobox transcription factors in promoting metastasis and malignancy, when overactive in adult animals. In this week’s Proceedings of the National Academies of Science, Robert Weinberg’s group has another paper to contribute to this story: The Spemann organizer gene, Goosecoid, promotes tumor metastasis.

Those following the area of Evo-Devo, or at least those that have read Carroll’s Endless Forms Most Beautiful, will remember that the Spemann’s organizer was originally identified as a cluster of cells capable of inducing and directing dramatic changes in the developing embryo. It was later identified that the unique properties of Spemann’s organizer were determined by transcription factors, which were categorized as homeobox genes.

Broad analogies between migrating tumor cells and migrating subpopulations of cells during embryonic development suggest that these processes have much in common. Common signal transduction pathways have been studied extensively for years, and the study of common transcriptional control mechanisms is rapidly catching up. As Hartwell et al. describe (below the fold):

Gastrulation is an embryonic developmental process that displays some striking similarities to tumor invasion and metastasis. This critical process establishes the basic body plan by way of highly coordinated cell movements and is initiated by a conserved group of cells originally characterized in Xenopus laevis as the Spemann organizer. In higher vertebrates, the organizer equivalents (e.g., the anterior primitive sreak in mouse and Hensen’s node in birds) are regions in which epithelial cells break their cell-cell junctions and ingress into the interior of the embryo, migrating as individual mesenchymal cells. This shift of cell phenotype is defined as an epithelial-mesenchymal transition (EMT).

Hartwell and colleagues found:

  1. Elevated levels of Goosecoid expression in Human breast tumors
  2. Goosecoid elicits an EMT and enhances cell motility
  3. TGF-beta signaling induces Goosecoid expression in adult breast epithelial cells
  4. Goosecoid enhances the metastatic ability of cancer cells

Further, they suggest that these findings “warrant a comprehensive examination of these genes in multiple types of human malignancies.” To that, I’d probably add study of inhibition of Goosecoid and other transcription factors more broadly.

Reference:

  • Hartwell KA, Muir B, Reinhardt F, Carpenter AE, Sgroi DC, Weinberg RA. The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Proc Natl Acad Sci U S A. 2006 Dec 1; 103(50):18969-74. Pubmed.

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