Jialing Xiang, Professor of Biology
For certain forms of cancer, two wrongs can make a right. That is the surprising discovery revealed in research by Illinois Tech Professor of Biology Jialing Xiang.
Xiang’s cancer investigations deal with the biological mechanisms designed to prevent the growth of tumor cells. One of the most important weapons in the body’s cancer-fighting arsenal is a specialized tumor suppressor gene known as Bax, which codes for an anti-cancer protein.
“Tumor suppressors like Bax are the cells’ police force,” Xiang says. When abnormal cells appear, the Bax protein attacks their power source, the mitochondria, terminating the diseased cells. This process of programmed cell death is known as apoptosis.
If something goes awry with the Bax gene, however, the suppressor’s tumor-fighting abilities are disabled. It has long been assumed that cancer patients who have a mutated Bax tumor protein due to a faulty Bax gene have a poor disease prognosis. But Xiang’s research suggests the picture is more complex.
As Xiang explains, there are two common processes that can disrupt the Bax gene, rendering its protective capability null and void. The first is a mutation in a specific coding region of the gene known as a microsatellite. Such regions carry multiple repeats of one of DNA’s four nucleotides—A, T, C, or G.
The multiple repeats found in microsatellite regions can sometimes confuse the gene production system that first transcribes the DNA sequence into RNA and then translates it into Bax protein. For example, eight Gs might mistakenly get transcribed as seven Gs—or perhaps nine. If these mistakes are not repaired in time, it will lead to a silencing of Bax expression, leaving the body vulnerable to tumor growth.
The second threat to Bax comes from a process known as alternative splicing. Before translation into a protein, the non-coding portions (or introns) of the Bax RNA are snipped out and the coding regions (or exons) are stitched together. Mistakes can happen with this stitching process, such that part of the exon is cut out as well, disrupting the Bax gene’s “reading frame,” which usually disables Bax gene expression.
But Xiang has discovered that something remarkable happens when both of these mistakes occur in tumor cells. When this happens, an alternate form of Bax known as Bax D2 can be created. This hybrid tumor suppressor gene appears to be even more potent than original Bax. The cancer cells with Bax D2 are selectively sensitive to certain chemotherapy drugs. Furthermore, Bax D2 only exists in tumor cells, not normal cells. The discovery has important implications for the selection of appropriate chemotherapy drugs and may serve as a new tumor marker, conferring improved prognosis and leading to targeted, less-toxic therapeutic approaches.
Xiang stresses that such basic research lays the critical groundwork necessary for clinical advances. “We spend so much time trying to kill cancerous cells,” she says. “We should spend a little more time understanding them and help cells find alternate means of repair.”
In further basic research, in 2015 Xiang and her collaborators solved a long-held mystery regarding how the protein kinase moves from the fluid inside the cell to the cell membrane, where it transmit signals. This discovery, which indicates the role of a small protein Ubl4A in creating “bridges” from the fluid to the membrane, holds promise for the development of better cancer therapeutics and for a better understanding of cell migration and wound healing. This work was published in the Proceedings of the National Academy of Sciences.