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Robert A. Weinberg. Hartwell, Kimberly A. (Kimberly Ann) Massachusetts Institute of Technology. Dept. of Biology. Massachusetts Institute of Technology. Department of Biology 2007-08-29T20:37:47Z 2007-08-29T20:37:47Z 2007 2007 http://hdl.handle.net/1721.1/38632 156999141 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2007. Vita. Includes bibliographical references (leaves 124-133). The process of invasion and metastasis during tumor progression is often reminiscent of cell migration events occurring during embryonic development. I hypothesized that genes controlling cellular changes in the Spemann organizer at gastrulation might be reactivated in tumors. The Goosecoid homeobox transcription factor is a known executer of cell migration from the Spemann organizer. I found that indeed Goosecoid is overexpressed in a majority of human breast tumors. Ectopic expression of Goosecoid in human breast cells generated invasion-associated cellular changes, including an epithelial-mesenchymal transition. TGF-03 signaling, known to promote metastasis, induced Goosecoid expression in human breast cells. Goosecoid induces the expression of E- cadherin SIP 1, scaffolding protein IQGAP 1, and PDGF signaling components, all which have independently been implicated in tumor metastasis. Moreover, Goosecoid significantly enhanced the ability of breast cancer cells to form pulmonary metastases in mice. These results demonstrate that Goosecoid promotes tumor cell malignancy and suggest that other conserved organizer genes may function similarly in human cancer. by Kimberly A. Hartwell. Ph.D. 133 leaves eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Biology. A role for the Spemann organizer gene, Goosecoid, in tumor metastasis Thesis application/pdf Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="4ded8eac-8e96-4232-b4fa-a6ee6785147b"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>A role for the Spemann organizer gene, Goosecoid, in tumor metastasis</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2007</PublicationDate> <Authors> <Author> <DisplayName>Hartwell, Kimberly A. (Kimberly Ann)</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biology.</Keyword> <Abstract>The process of invasion and metastasis during tumor progression is often reminiscent of cell migration events occurring during embryonic development. I hypothesized that genes controlling cellular changes in the Spemann organizer at gastrulation might be reactivated in tumors. The Goosecoid homeobox transcription factor is a known executer of cell migration from the Spemann organizer. I found that indeed Goosecoid is overexpressed in a majority of human breast tumors. Ectopic expression of Goosecoid in human breast cells generated invasion-associated cellular changes, including an epithelial-mesenchymal transition. TGF-03 signaling, known to promote metastasis, induced Goosecoid expression in human breast cells. Goosecoid induces the expression of E- cadherin SIP 1, scaffolding protein IQGAP 1, and PDGF signaling components, all which have independently been implicated in tumor metastasis. Moreover, Goosecoid significantly enhanced the ability of breast cancer cells to form pulmonary metastases in mice. These results demonstrate that Goosecoid promotes tumor cell malignancy and suggest that other conserved organizer genes may function similarly in human cancer.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>