This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cancer is one of the leading causes of death of all mankind. Cancer cells not only display uncontrolled proliferation, but also develop the ability to migrate from their original site to other organs in the body. This event is known as metastasis, the hallmark of malignant cancers. During metastasis, cancer cells break numerous barriers to travel through the body's circulatory system and invade other organs to form secondary tumors. Therefore, it is important to understand, the underlying mechanism of cancer metastasis to find a cure for cancer. Integrins, membrane protein receptors for extracellular matrix proteins, have been implicated in cancer cell proliferation and metastasis. In addition, focal adhesion kianse (FAK) has been shown to be pivotal for cell adhesion and migration. However, the involvement of effector molecules which lie in the integrin and FAK mediated signaling pathway is largely unknown. Our lab recently discovered an ubiquitously expressed calcium and integrin-binding protein 1 (CIB1) which interacts with a number of cellular proteins, including platelet specific integrin ?IIb?3. Further, CIB1 also interacts and co-localizes with FAK at the membraneous extensions and has been implicated in cell spreading and migration. The role of CIB1 in a pathophysiological condition such as cancer remains to be elucidated. Our preliminary results show that CIB1 expression is significantly increased in breast cancer tissue compared to normal breast tissue. Overexpression of CIB1 in T47D cells, breast epithelial cell line, showed increased cell migration on collagen matrix as determined by a trans-well migration assay. When endogenous CIB1 was knocked down in T47D cells using siRNA, cell migration was significantly decreased. A decreased tyrosine phosphorylation of FAK was also observed in CIB1 knocked down T47D cells compared to mock transfected cells as determined by Western blot analysis, demonstrating that CIB1 may mediate cancer cell migration by enhancing phosphorylation of FAK. The goal of the present study is to have better insights of CIB1's role in cancer cell invasion leading to metastasis. This will be achieved by determining the relationship of CIB1 expression and invasive behavior of the breast cancer cells in vitro and vivo and by elucidating the signaling pathways that CIB1 regulates in order to dictate the invasive behavior of breast cancer cells. We believe that our study will give a better understanding of the role of CIB1 in cancer cell invasion. It will also identify a novel cellular target for therapeutic intervention of breast cancer. Further, a clearer understanding of this process will provide a basis for developing effective therapies for this most lethal aspect of breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016472-11
Application #
8359619
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2011-03-01
Project End
2012-02-29
Budget Start
2011-03-01
Budget End
2012-02-29
Support Year
11
Fiscal Year
2011
Total Cost
$116,891
Indirect Cost
Name
University of Delaware
Department
Type
Organized Research Units
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
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