Metastasis is the main cause of death in cancer patients. It is the spread of cancer cells from the primary tumor to distant organs and this process requires the ability to degrade the basement membrane and extracellular matrix (ECM). Tumor cells obtain this ability through the formation of membrane protrusions called invadopodia. They are actin-rich subcellular structures that contain a number of regulatory and adaptor proteins in order to recruit proteases, such as metalloproteinases, MMP2 and MMP9, MT1-MMP, to carry out ECM degradation. Our past work demonstrates that invadopodia are essential for tumor metastasis. Given this idea, targeting invadopodia formation in tumor cells is a potential anti-metastasis treatment. Past research on anti-metastasis therapy focused on targeting MMPs because of their direct role in ECM degradation. Although MMP inhibitors demonstrated promising results in preclinical trials, they failed in clinical trials due to broad spectrum of inhibition and toxicity. An alternative to targeting MMPs is to target proteins that ar involved in invadopodia assembly. In this proposal, I aim to better understand invadopodia assembly and how proteases are recruited to invadopodia by performing immunoprecipitation experiments followed by mass spectrometry. In addition, degradation assays, immunocytochemistry, and in vivo studies will be performed to understand the role of the identified protein in invadopodia-mediated metastasis.

Public Health Relevance

Metastasis is the number one cause of death in breast cancer patients. Tumor cells can form structures called invadopodia to gain migratory and invasive abilities to spread to distant organs. Understanding what factors regulate invadopodia function and testing their importance on tumor cell metastasis will aid in the development of anti-metastatic drugs and reduce the number of metastasis-related deaths.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA200271-03
Application #
9285746
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Schmidt, Michael K
Project Start
2015-08-01
Project End
2018-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093