Researchers at University of California San Diego have discovered a process in which liver cells share molecules via vesicle exchange in order to multiply under conditions that would ordinarily suppress cell proliferation. They also found evidence that this process occurs in various types of cancer cells, paving the way for a new approach to tackling treatment resistance in cancer. The findings were published on October 17, 2023 in eLife.
The body has many molecular processes in place to help control cell proliferation, turning it on and off as necessary in different circumstances and in different organs. This is well-exemplified by the liver, which has a high capacity for regeneration to support its important detoxification and metabolic functions.
In previous research, Feng and his team observed that a minority of liver cells in mice could still proliferate even when the cells were genetically engineered to lack a critical signaling enzyme required for cell proliferation. This enzyme, called Shp2, helps liver cells know when it’s time to divide during liver regeneration. Shp2 is also a known target for treating various cancers, and Shp2 inhibitors are involved in several ongoing clinical trials.
While the researchers made the discovery in noncancerous liver cells, they also uncovered evidence that cancer cells may use the same strategy to resist treatment and continue to divide. The vesicles that liver cells use to share molecules are marked by a protein called CD133, and the researchers also detected abnormally high amounts of this protein in a variety of human cancer cells.
While the findings could lead to the discovery of new cancer therapies, they also suggest a new way of thinking about cancer initiation, progression and recurrence. CD133 is widely viewed as a marker of cancer stem cells, groups of cancer cells that are thought to be responsible for initiating tumors.
Co-authors include: Kota Kaneko, Yan Liang, Qing Liu, Shuo Zhang, Alexander Scheiter and Dan Song, all at UC San Diego.
This study was funded, in part, by the National Institutes of Health (grants R01DK128320, R01CA236074 and R01CA239629) and Deutsche Forschungsgemeinschaft (grant 502688960).
(AM/Newswise)
