Deliang Cao, PhD
Dr. Cao is an Associate Professor in the Department of Medical Microbiology, Immunology and Cell Biology at SIU School of Medicine and a member of the Simmons Cancer Institute. Dr. Cao is a member of the American Association of Cancer Research and a member of the American Society for Biochemistry and Molecular Biology.
Physiopathological Function of Aldo-Keto Reductase 1B10 (AKR1B10)
AKR1B10 is a main research project ongoing in my laboratory that has been supported by NCI and DoD Breast Cancer Research Program. We have published 16 peer-reviewed research articles plus several review article on AKR1B10, leading the AKR1B10 studies internationally.
AKR1B10 is a new member of aldo-keto reductase (AKR) superfamily that we first isolated in human hepatocellular carcinoma (HCC). In human normal tissues, AKR1B10 is specifically expressed in epithelial cells of the gastrointestinal tract (GT), with a detectable level in the liver. AKR1B10 is not expressed in the breast and lung. In diseased tissues, AKR1B10 is upregulated in breast, lung and colon cancers but oppositely, down regulated in ulcerative colitis (UC) and colitis-associated colorectal cancers. The essential biological functions of AKR1B10 described thus far include 1) a NADPH-dependent reductase, reducing carbonyl groups, and 2) a mediator of long chain fatty acid de novo synthesis. Our studies on AKR1B10 focus on two fields:
(a) AKR1B10 as a oncogenic promoter of breast cancer
We found that AKR1B10 is overexpressed in breast cancer and promotes growth and metastasis of breast cancers to lymph nodes. Through clearance of electrophilic carbonyls metabolically produced in tumor cells, AKR1B10 protects the host cells from carbonyl and subsequent oxidative damage. By promoting long chain fatty acid/lipid synthesis, AKR1B10 activates lipid second messenger-mediated PKC/ERK signaling pathway, promoting tumor cell proliferation, migration and invasion. We are currently digging the possibility of developing AKR1B10-target therapeutics or molecular diagnosis for breast cancer.
(b) AKR1B10 as a regulator of colonic epithelium
AKR1B10 is primarily expressed in colon epithelial cells, but its expression is diminished or lost in UC and UC-associated colorectal cancer. Colonic epithelium is featured with (1) constant self-renewal and (2) carbonyl stress derived from diets and luminal microbes. Our studies demonstrated that AKR1B10 specifically expressed in the epithelial cells of colon promotes their proliferation and migration, and protects them from carbonyl lesions. AKR1B8 (an ortholog of human AKR1B10 in the mouse) knockout leads to diminished epithelial proliferation and injury repair, as well as increased DNA damage of the colonic epithelium. The colonic mucosa of AKR1B8 mice was highly susceptible to dextran sodium sulfate (DSS)-induced colitis and colitis (inflammation)-associated cancer. We are currently digging the underlying mechanisms
Tumor suppressive role of NF-κB RelA/p65
NF-KB RelA/p65 has long been recognized as an oncogenic transcriptional factor and a target for anticancer therapy. Evidence is emerging recently that RelA/p65 functions as a tumor suppressor, but the underlying mechanisms are not well known. Studies in our laboratory have shown that phosphomimetic mutation at Ser536 of RelA/p65 gene induces dramatic apoptosis and senescence through changing the expression of a large group of cell death and survival genes. Our testing hypothesis is that phosphorylation and activation of specific sites in RelA/p65 may switch the face of RelA/p65 as an oncogene or a tumor suppressor.
Experimental therapeutics and drug resistance
Chemotherapy still stands for a main option for patients with late stage cancers when a targeted therapy is unavailable or becomes resistant. Using gene transfer, RNA interference, and gene knockout technologies, we investigate the metabolic pathways and molecular mechanisms affecting antitumor activity and tumor selectivity of cytotoxic agents, i.e., fluoropyrimidines and anthracyclines. For translations, we explore rapid, easy methods to monitor activity of the metabolic pathways and effectors. Our final goal is to provide evidence and methodologies for the individualization of the chemotherapeutic agents.
- ARL-1 SPECIFIC ANTIBODY (U.S. Application #: 12/032327; Patent #: 8114604，02/14/2012)
- METHODS FOR DIAGNOSING BOWEL DISEASE (U.S. Application #: 12/739371, 10/24/2008; Patent #: 8551720，10/08/2013)
- ARL-1 SPECIFIC ANTIBODIES AND USES THEREOF (U.S. Application #: 13/017618，01/31/2011; ; Patent #: 8685666，04/01/2014)