The University of Toledo Translation Journal of Medical Sciences 
Haematology/Oncology Abstract, Department of Medicine Research Symposium UTJMS 2023 May 5; 11(1):e1-e1 

Characterization of the Novel IQGAP1-Adrenergic 
Receptor Pathway in Lung Cancer 

Omar Abdul-Aziz1*, Yusuf Barudi1, and Mahasin A. Osman1 

1Division of Haemtology and Oncology, Department of Medicine, The University of 
Toledo, Toledo, OH 43614 

*Corresponding author: Omar.Abdul-Aziz@rockets.utoledo.edu

Published: 05 May 2023 

Lung cancer is the leading cause of cancer death for both men and women making up almost a quarter of 
all cancer-related death in the United States. The IQ-motif containing Ras GTPase-activating-like 
(IQGAP1) protein is a ubiquitously expressed protein in humans. IQGAP1 is a signaling scaffold 
involved in regulating various cellular functions ranging from organization of the actin cytoskeleton, 
transcription, and cellular adhesion to regulating the cell cycle and secretion. Chronic activation or 
inhibition of IQGAP1 both leads to a myriad of diseases, including cancer and diabetes. We employ a 
pharmacogenetic approach to define mechanisms of IQGAP1 in such diseases and identify potential 
therapeutics. Our studies revealed that yeast cells lacking IQGAP1, the homolog of human IQGAP1, had 
diminished cell growth when treated with norepinephrine (NE), suggesting that NE works through 
IQGAP1. The Alpha-2A-Adrenergic receptor (α-2ADR) is a known target of NE that we recently found 
differentially expressed in various lung cancer cell lines and interacts with IQGAP1. To begin 
characterizing this pathway, we determined dose effect of NE on proliferation of human lung cancer 
cells and identified an optimal dose (IC50) of NE.  Next, we evaluated the effect of that dose on the gene 
expression levels of the two proteins and a downstream transcription factor, Nuclear Respiratory Factor 
1 (NRF1), comparing response of lung cancer cells with normal lung epithelia by qRT-PCR. Our results 
showed that while NE significantly downregulated the α -2ADR mRNA in normal cells, it caused a 
slight increase in some cancer cells. Our ongoing research will examine the effect of NE on protein 
levels and localizations in lung cancer and IQGAP1 mutant cells, as well as on the activity of signaling 
components downstream of IQGAP1. Our findings have significance in precision medicine. 

https://dx.doi.org/10.46570/utjms.vol11-2023-731 

https://dx.doi.org/10.46570/utjms.vol11-2023-731
mailto:Omar.Abdul-Aziz@rockets.utoledo.edu