This proposal will test the hypothesis that kallikrein 6 (KLK6) protein is functionally involved in, and may be a useful marker of, colon carcinogenesis. We have shown that: 1) KLK6 protein can be detected at the adenomas in the mouse colon, and in human colon tumors;2) KLK6 function blocking antibody attenuates invasion of colon cancer cells;and 3) colon cancer cells with knockdown of KLK6 do not form distant metastases in SCID mouse model and increase animal survival rates. To test the overall hypothesis, we propose the following specific aims: 1) determine the role of KLK6 in the colon cancer progression in vivo;2) determine the role of KLK6 in colon cancer metastasis;3) evaluate KLK6 protein expression and enzymatic activity in the colon. The major objectives of this proposal are to determine the role of KLK6 in colon tumor and metastasis formation, develop an imaging modality for measuring of KLK6 enzymatic activity in the colon and correlate it with disease progression.

Public Health Relevance

Colorectal cancer (CRC) is the third most common cancer in the United States. Screening for colon cancer has the ability to reduce mortality from this disease. Many kallikreins have been identified as promising diagnostic and/or prognostic biomarkers for several cancer sites, including ovarian, breast and prostate. In colon cancer, KLK6 expression is likely to be involved in tumor progression and metastasis through degradation of the extracellular matrix. This proposal will generate data on KLK6 functions and enzymatic activity in colon cancer. It will evaluate KLK6 as a specific molecular marker for colon cancer progression, metastasis and targeted therapy.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA157595-03
Application #
8658402
Study Section
Tumor Progression and Metastasis Study Section (TPM)
Program Officer
Ault, Grace S
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Arizona
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Basu Roy, Upal K; Henkhaus, Rebecca S; Loupakis, Fotios et al. (2013) Caveolin-1 is a novel regulator of K-RAS-dependent migration in colon carcinogenesis. Int J Cancer 133:43-57
Ignatenko, Natalia A; Gerner, Eugene W (2013) Get the fat out! Cancer Prev Res (Phila) 6:161-4