UCLA Health Jonsson Comprehensive Cancer Center researchers discovered for the first time that a gene commonly associated with massive axonal neuropathy, a rare and severe neurological disorder, also inhibits aggressive tumor cell proliferation in head, neck cancer.
The scientists discovered that when a specific genetic variant (GAN gene exon 8 SNP T allele) of the GAN gene is absent, certain proteins are produced, increasing the likelihood of cancer cells spreading and becoming treatment resistant.
These findings imply that the existence of the genetic variation and higher expression of the GAN gene product gigaxonin may contribute to better survival in head and neck tumors and might potentially be utilized as diagnostic markers for identifying.
Background
There are several neurological illnesses that are linked to an increased risk of cancer. This elevated risk is frequently related with gene mutations that impair the cell’s ability to repair DNA effectively. Giant axonal neuropathy, a rare genetic illness that causes gradual damage to the peripheral nerves and central nervous system, is caused by mutations in the GAN gene, which result in the loss of expression of the gigaxonin protein.
This protein is critical for the structural integrity of cells. In prior investigations on head and neck cancer, UCLA researchers discovered that gigaxonin interacts with p16 to add ubiquitin to NF-κB. This process, known as ubiquitination, is how cells control the function of proteins. However, the exact role of gigaxonin in cancer is not well established. The authors demonstrate that ubiquitination of NF-κB leads to downregulation of Snail, a protein involved in epithelial to mesenchymal transition (EMT), also known as metastasis. Thus, the expression of gigaxonin inhibits the aggressive development of human cancer cells.
Method
This protein is critical for the structural integrity of cells. In prior investigations on head and neck cancer, UCLA researchers discovered that gigaxonin interacts with p16 to add ubiquitin to NF-κB. This process, known as ubiquitination, is how cells control the function of proteins. However, the exact role of gigaxonin in cancer is not well established. The authors demonstrate that ubiquitination of NF-κB leads to downregulation of Snail, a protein involved in epithelial to mesenchymal transition (EMT), also known as metastasis. Thus, the expression of gigaxonin inhibits the aggressive development of human cancer cells.
Impact
The work sheds light on the molecular pathways driving head and neck cancer growth. If verified in subsequent research, the use of gigaxonin as a diagnostic marker.
Journal
The findings appeared in Cancer Research Communications, a magazine published by the American Association for Cancer Research.
Eri Srivatsan, a professor of surgery at the Veterans Affairs Greater Los Angeles Healthcare System (VA GLAHS) Medical Center and UCLA’s David Geffen School of Medicine, and Dr. Daniel Shin, an assistant professor of medicine at the VA GLAHS Medical Center and David Geffen School of Medicine, are the co-senior authors. Both are affiliated with UCLA Health’s Jonsson Comprehensive Cancer Center and the Molecular Biology Institute. The study’s first author is Mysore Veena, a scientist at the Geffen School of Medicine. UCLA authors include Jungmo Gahng, Dr. Mustafa Alani, Albert Ko, Saroj Basak, Isabelle Liu, Kimberly Hwang, Jenna Chatoff, Natarajan Venkatesan, Marco Morselli, Weihong Yan, Ibraheem Ali, Karolina Elżbieta Kaczor-Urbanowicz, Bhavani Shankara Gowda, Patrick Frost, Matteo Pellegrini, and Dr. Neda Moatamed.
Reference Article- Potential Genetic Marker Boosts Survival in Head, Neck Cancer