Investigation of the role of IQGAP1 in metastasis
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2004.
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| Format: | Thesis |
| Language: | en_US |
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Massachusetts Institute of Technology
2005
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| Online Access: | http://hdl.handle.net/1721.1/27045 |
| _version_ | 1826206972726214656 |
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| author | Frew, Sarah Elizabeth Ann, 1976- |
| author2 | Richard O. Hynes. |
| author_facet | Richard O. Hynes. Frew, Sarah Elizabeth Ann, 1976- |
| author_sort | Frew, Sarah Elizabeth Ann, 1976- |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2004. |
| first_indexed | 2024-09-23T13:41:49Z |
| format | Thesis |
| id | mit-1721.1/27045 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:41:49Z |
| publishDate | 2005 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/270452019-04-11T06:53:38Z Investigation of the role of IQGAP1 in metastasis Frew, Sarah Elizabeth Ann, 1976- Richard O. Hynes. Massachusetts Institute of Technology. Dept. of Biology. Massachusetts Institute of Technology. Dept. of Biology. Biology. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2004. Includes bibliographical references (leaves 108-124). Metastasis, or the spread of a primary tumor to distal sites in the body, is the major cause of human cancer-related morbidity and mortality. Metastasis requires a complex series of cellular events that remain poorly understood at the molecular level. Recently, advances in microarray technology have allowed cancer biologists to globally survey metastatic progression and define patterns of gene expression that correlate with progression to a metastatic phenotype. By using such a genomic approach, our laboratory identified a subset of genes that regulate the actin cytoskeleton whose enhanced expression correlates with metastasis. This thesis describes the characterization of IQGAP1, a key regulator of the cytoskeleton, as a potentially critical player in metastatic progression. Here I show a strong positive correlation between IQGAP1 expression levels and metastatic progression in both in vivo-selected human metastatic melanoma cells and other human tumors. In addition, I have experimentally analyzed the role of IQGAP1 in metastasis using two different dominant-negative mutants. The results suggest that IQGAP1 may play a functional role in metastatic progression, particularly in the processes of cell migration and invasion. This work lays a scientific framework by which cancer biologists can look at global gene expression analyses and then probe deeper into individual genes to define the molecular mechanisms underlying their roles. In addition, this work contributes to a deeper understanding of the molecular pathogenesis of metastasis, and identifies in IQGAP 1 a potential molecular target for future tumor metastasis therapies. by Sarah Elizabeth Ann Frew. Ph.D. 2005-09-06T21:27:42Z 2005-09-06T21:27:42Z 2004 2004 Thesis http://hdl.handle.net/1721.1/27045 56795014 en_US 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 124 leaves 7626998 bytes 7642227 bytes application/pdf application/pdf application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biology. Frew, Sarah Elizabeth Ann, 1976- Investigation of the role of IQGAP1 in metastasis |
| title | Investigation of the role of IQGAP1 in metastasis |
| title_full | Investigation of the role of IQGAP1 in metastasis |
| title_fullStr | Investigation of the role of IQGAP1 in metastasis |
| title_full_unstemmed | Investigation of the role of IQGAP1 in metastasis |
| title_short | Investigation of the role of IQGAP1 in metastasis |
| title_sort | investigation of the role of iqgap1 in metastasis |
| topic | Biology. |
| url | http://hdl.handle.net/1721.1/27045 |
| work_keys_str_mv | AT frewsarahelizabethann1976 investigationoftheroleofiqgap1inmetastasis |