When graduate student Xiaojun Tan first noticed the epidermal growth factor receptors within the cancer cell, he was surprised. These receptors always branched off the cell’s surface, and had never been observed within the cell quite like this before. Yet, here in these chemically starved cancer cells, an inactive collection of these receptors had accumulated.
“I was very excited,” Tan said of the discovery. “But at the same time, I also doubted it.”
The EGF receptor is a protein receptor that is generally located along the cell’s membrane, or outer wall. There, it plays a role in cell communication that eventually leads to the growth and division of a cell.
In cancer cells, the EGF receptor is often overexpressed, or more present and active. This leads to unregulated growth among cancer cells and, ultimately, the spread of cancer.
Drug treatments often try to target the EGF receptor. Pharmaceutical companies have invested billions of dollars in treating and inhibiting the EGF receptor according to Professor Richard A. Anderson, Tan’s mentor and a co-author of his research paper. The treatments have largely been unsuccessful.
Almost by accident, Tan may have found why these treatments weren’t working. While looking to observe the relationship between the protein LAPTM4B and EGF receptors, he found treated and inactive EGF receptors collected within a part of the cell that triggered a “self-eating” mechanism called autophagy.
Most cells use autophagy as a survival mechanism to get them through hard times. By recycling proteins, autophagy allows the cell to maintain energy levels through starvation. In cancer cells, this means treated cells have a way to hold out through treatment.
According to Tan, cell starvation promoted the interaction between LAPTM4B and the EGF receptor, which led to the inactive EGF receptor being used to initiate autophagy.
“That has never been published before. I was very surprised,” said Tan.
His skepticism and surprise were shared by his mentor. “When [Tan] first showed me this, I said ‘No, I don’t believe that. That’s weird. And that’s a tough thing for a mentor to say to a student,” said Anderson.
Yet, rather than brush off the observation, Anderson allowed Tan to pursue it further.
“I had my own predictions, and I’m often wrong. So I said, ‘Yeah! Go ahead and work on this!’ … There should be a lot of freedom to explore new ideas for students,” said Anderson.
According to Anderson, it is possible that Tan’s findings could lead to a new approach to treating epithelial cancers.
The National Library of Medicine attributes roughly 30 percent of epithelial cancers to mutations in the EGF receptor. Epithelial cancers account for 80 to 90 percent of all cancers, according to the National Cancer Institute.
While using EGF receptor inhibitors has been a research focus for a while now, Tan’s findings show that inhibiting EGF receptors alone won’t work. On the other hand, according to Anderson, pairing the EGF receptor with an autophagy inhibitor or something that targets the LAPTM4B protein could lead to a different story for a patient.
It’s only a matter of time before the results of Tan’s discovery begin to manifest themselves in clinics, according to Anderson. Inhibitors for autophagy already exist in the form of chloroquine, a drug discovered in 1934 whose derivatives are used to treat malaria.
Anderson attests this discovery to the nature of basic science labs, labs where studies range from cell structure to mating flies.
“I think it’s a great example of how basic science can impact the human condition,” said Anderson. “In the long run, I think it’ll have substantial impact in the way cancer treatment is studied.”
Tan, who began his research with the ultimate goal of improving cancer treatment and diagnosis, reflected on his surprising discovery. “Enjoy difficult or unexpected situations,” he said. “That is when we make more progress.”
Tan’s research, co-written by Anderson, Narendra Thapa and Yue Sun, was published earlier this month in the scientific journal Cell. This research was conducted with support from the National Institutes of Health, the Howard Hughes Medical Institute International Student Research Fellowships and the American Heart Association.
