The results of a study led by Dr. Shujun Liu, head of the Cancer Epigenetics and Experimental Therapeutics section at The Hormel Institute, were published in the high impact journal Oncogene this week. Dr. Liu’s study shows that DNA methyltransferases (DNMT) and receptor tyrosine kinases (RTK) create a vicious circle that acts as a key regulator of cell fate decision in lung cancer development, and represents an attractive target for designing innovative therapeutic strategies. The article, “A regulatory circuit composed of DNA methyltransferases and receptor tyrosine kinases controls lung cancer cell aggressiveness” was a collaboration with other researchers from Mayo Clinic and University of Louisville, including Drs. Fei Yan, Na Shen, Jiuxia Pang, Na Zhao, Bo Deng, Bing Li, Yanan Yang, Ping Yang and Julian R. Molina.
Lung cancer is the second most common cancer in both men and women. It is estimated that about 14% of all new cancers are lung cancers. In the United States, in 2017 over 220,000 new cases of lung cancer were identified and about 160,000 deaths from lung cancer were reported. However, the molecular mechanisms underlying aggressive lung cancer remain largely elusive, and scientists, doctors, and patients are always looking for new therapeutic regimens.
Most of the research into lung cancer has viewed abnormal DNA methylation and the deregulated kinase signaling as single entities, and there is little known about whether and how DNMTs and RTKs work together to orchestrate tumor development in lungs. In this study, Dr. Liu and his team dissected the regulatory and functional interactions between DNMTs and RTKs in lung cancer development.
“Our study provides the first evidence that aberrant DNA methylation (epigenome) and hyperactive tyrosine kinase signaling (kinome) form a regulatory circuit in lung cancer cells, and cooperatively propel lung tumorigenesis and metastasis. Not only do these findings add a new layer to the complexity of molecular processes regulating lung cancerous lesions, but also highlight the capability of tyrosine kinases to modulate DNA methylation; in turn, DNA methyltransferases to alter kinase cascades,” said Dr. Shujun Liu.
“Because dual-genetic and dual-pharmacological disruption of this vicious circle led to a more profound inhibition of tumor cell growth in vitro and in vivo, our findings highlight the epigenome-kinome interplay as a promising therapeutic target, providing a widely applicable approach to treat lung cancer.”