If it were possible to reduce the vigor with which cancer cells migrate, curtailing their penetration of nearby blood vessels and neighboring tissues, the cells would be far less dangerous, and cancer itself far less deadly. To find ways to slow the spread of cancer, scientists have been investigating why certain cancer cells may remain homebodies, or turn into bold wanderers.
A group of researchers at the University of Bristol and the University of Birmingham, while studying breast and prostate cancer cells, found that a particular cellular mechanism enhances cancer’s ability to spread. This mechanism involves a transcription factor known as proline-rich homeodomain protein, or PRH. If PRH levels are low, or if PRH’s subcellular distribution is unfavorable—that is, if PRH is relatively unavailable in the nucleus—cancer cells migrate faster. To confirm this finding, the scientists also determined that without PRH, cancer cells move through a porous gel more efficiently.
Scientists have been aware of PRH’s role in controlling cell growth and specification for some time. For example, it is essential for the healthy development of fetuses, but this is the first time PRH has been implicated in the movement of cancer cells.
The new results were published November 18 in Oncology, in a paper entitled “PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin.” As the paper’s title suggests, its authors considered how low levels of PRH could increase cell migration.
After noting that previous work showing that transforming growth factor-β co-receptor Endoglin inhibits the migration of prostate and breast cancer cells, the paper’s authors stated that their work showed PRH can bind to the Endoglin promoter in immortalized prostate and breast cells. “PRH overexpression in these cells results in increased Endoglin protein expression,” they wrote. “PRH knockdown results in decreased Endoglin protein expression.”
“Moreover, we demonstrate that Endoglin overexpression abrogates the increased migration shown by PRH knockdown cells. Our data suggest that PRH controls the migration of multiple epithelial cell lineages in part at least through the direct transcriptional regulation of Endoglin.”
Reflecting on the significance of these findings, one of the study’s authors, Kevin Gaston, Ph.D., reader at Bristol’s School of Biochemistry, said, “It is not simply the growth of cancers but their ability to move to multiple locations in the body that makes the disease so deadly. PRH transcription factor inhibits the migration of normal and cancerous breast cells and prostate cells and this represents a novel mechanism that could be important in multiple cancers.”
Another study author, Padma-Sheela Jayarman, Ph.D., senior lecturer at the University of Birmingham, noted that the scientists’ work revealed new targets for translational research. Because the same mechanism was identified in more than one type of cancer cell, PRH regulation of Endoglin may represent not only a novel method for controlling migration, but also a means to treat multiple cancers.