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Article
Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells
FIU Electronic Theses and Dissertations
  • Nicole Porther, Biological Sciences
Document Type
Dissertation
Degree
Doctor of Philosophy (PhD)
Major/Program
Biology
First Advisor's Name
Manuel Barbieri
First Advisor's Committee Title
Committee Chair
Second Advisor's Name
Marianna Baum
Second Advisor's Committee Title
Committee Member
Third Advisor's Name
Lidia Kos
Third Advisor's Committee Title
Committee Member
Fourth Advisor's Name
Ophelia Weeks
Fourth Advisor's Committee Title
Committee Member
Fifth Advisor's Name
Fernando Noriega
Fifth Advisor's Committee Title
Committee Member
Keywords
  • migration,
  • invasion,
  • Rab GTPases,
  • endocytosis,
  • receptor trafficking,
  • IGFR,
  • caveolin
Date of Defense
3-20-2015
Abstract

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases, are small signaling molecules and critical in the regulation of many cellular processes including cell migration, growth via the endocytic pathway. This research involves the role of Rab GTPases, specifically Rab5 and its guanine exchange factors (GEFs), in the promotion of cancer cell migration and invasion. Two important questions abound: Are IGFR stimulation and downstream effect involved the endocytic pathway in carcinogenesis? What role does Rab5 play in cell migration and invasion of cancer cells? The hypothesis is that growth factor signaling is dependent on Rab5 activity in mediating the aggressiveness of cancer cells. The goal is to demonstrate that IGF-1 signaling is dependent on Rab5 function in breast cancer progression. Here, the results thus far, have shown that while activation of Rab5 may mediate increased cell proliferation, migration and invasion in breast cancer cells, the Rab5 GEF, RIN1 interacts with the IGFR thereby facilitating migration and invasion activities in breast cells. Furthermore, endocytosis of the IGFR in breast cancer cells seems to be caveolin dependent as the data has shown. This taken together, the data shows that IGF-1 signaling in breast cancer cells relies on IGF-1R phosphorylation, caveolae internalization and sequestration to the early endosome RIN1 function and Rab5 activation.

Identifier
FI15050202
Citation Information
Nicole Porther. "Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells" (2015)
Available at: http://0-works.bepress.com.library.simmons.edu/nicole_porther_chang/10/