It is estimated that over 140,000 people in the United States will be diagnosed with cancer of the colon and rectum and approximately 51,000 deaths will occur from this disease in 2010. The majority of colon cancer-related deaths can be attributed to metastasis. Therefore, a better understanding of the metastatic process may lead to prognostic and therapeutic advancements. Epidermal growth factor receptor (EGF-R) and Hedgehog (Hh) signaling pathways are independently known to contribute to the development or progression of many cancers including malignancies of the skin, brain, lung, breast, prostate, pancreas, ovary, and colon. Several studies now support the notion that bi- directional cross-talk between Hh and EGF-R can dramatically alter the cellular effects of either pathway alone. However, the implication of these complex interactions in regard to the development, progression, prognosis, and treatment of cancer remain largely unexplored. The goal of this research plan is to determine the contribution of EGF-R and Hh signaling interactions to the progression and metastasis of human colon cancer cells.
The specific aims are to 1) Determine the effects of EGF-R on Hh mediated colon cancer cell signaling, growth, and survival, and to 2) Determine how EGF-R and Hh signaling modulates growth, survival, and spontaneous metastasis of human colon cancer cells growing orthotopically in mice. The K01 award would support Dr. Rebhun's career development and will further prepare him for an independent research career in comparative and translational cancer research. Dr. Rebhun is a board certified clinical veterinary oncologist (DVM, Diplomate ACVIM-Oncology) and is a dual-trained clinician/scientist with a Ph.D. degree in cancer biology. Five years of mentored support is requested.

Public Health Relevance

(provided by applicant): Colon cancer is the third most common cause of cancer related death in both men and women and it is estimated that over 50,000 people will die of this disease within the United States in 2010. A better understanding of colon cancer cell signaling and metastasis is required in order to advance treatment of this disease. The goal of this project is to understand and describe interactions between specific cell signaling pathways that have individually been implicated in the progression of colon cancer.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01RR031272-01A1
Application #
8189593
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Contreras, Miguel A
Project Start
2011-07-15
Project End
2016-05-31
Budget Start
2011-07-15
Budget End
2012-05-31
Support Year
1
Fiscal Year
2011
Total Cost
$130,950
Indirect Cost
Name
University of California Davis
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Withers, Sita S; York, Daniel; Johnson, Eric et al. (2018) In vitro and in vivo activity of liposome-encapsulated curcumin for naturally occurring canine cancers. Vet Comp Oncol 16:571-579
Rebhun, R B; Kass, P H; Kent, M S et al. (2017) Evaluation of optimal water fluoridation on the incidence and skeletal distribution of naturally arising osteosarcoma in pet dogs. Vet Comp Oncol 15:441-449
Shahi, Mehdi Hayat; York, Daniel; Gandour-Edwards, Regina et al. (2015) BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance. PLoS One 10:e0131006
Shahi, Mehdi Hayat; Holt, Roseline; Rebhun, Robert B (2014) Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells. PLoS One 9:e96593
Seo, Kyoung won; Holt, Roseline; Jung, Yong-Sam et al. (2012) Fluoroquinolone-mediated inhibition of cell growth, S-G2/M cell cycle arrest, and apoptosis in canine osteosarcoma cell lines. PLoS One 7:e42960