Scientists at the A*STAR Institute of Molecular and Cellular Biology have found that a normal cell process is disrupted by the over expression of a specific protein, and that disruption causes cancer cells to grow aggressively. The role of this phosphatase protein in promoting the self-destruction of healthy cells and the progression of ovarian cancer has been further revealed in a series of experiments by researchers at A*STAR. The protein, called PTP4A3, is known to be overexpressed in cancer cells and researchers are hopeful that it could be useful as a biomarker for disease prognosis.
In any form of cancer, the process of unhealthy tumor cells growing and spreading is caused in part by the exploitation of some of the body's natural cellular processes. One example of such a process is the self-destruction and recycling of older or damaged cells in the body. This process is known as autophagy and is normal and necessary for keeping healthy cells alive in the body.
Autophagy is carried out by organelles known as autophagosomes, whose job is to take apart cells and transport the unwanted cellular material to be recycled into new membranes and proteins. This constant dismantling and recycling is what keeps cells healthy.
Autophagosomes go through a maturation process during autophagy, which allows them to carry out their role effectively.
Through performing a series of experiments investigating the role of PTP4A3 in cancer progression, Qi Zeng and co-workers at the A*STAR Institute of Molecular and Cell Biology in Singapore, together with other scientists in Singapore and the UK, have uncovered links between the overexpression of PTP4A3 and the acceleration of autophagosome maturation that occurs during autophagy. Apparently, speeding up the maturation process of the autophagosomes can lead to the rapid spread of ovarian cancer cells.
"Our experiments on the expression of PTP4A3 in ovarian cancer cells led us to discover that the protein exploits the autophagy pathway in order to promote cancer cell growth," says Zeng.
The researchers found that PTP4A3 accumulates in autophagosomes, accelerating the maturation process. This in turn encourages the destruction of healthy cells and allows the cancer to take hold. When autophagosomes mature at an accelerated rate, they demolish healthy cells, in addition to the older and damaged cells that are their intended targets. Unexpectedly, Zeng and her team also discovered that PTP4A3 itself then submits to autophagy at a later stage. After the cancer has progressed dangerously, the same process that caused it to flourish then begins to destroy the cells containing PTP4A3.
Following analysis of a large set of data taken from ovarian cancer patients, the team found that high levels of PTP4A3 together with autophagy genes were significantly correlated with poor prognosis in human ovarian cancer patients. "This means that PTP4A3 levels could potentially act as a useful biomarker for prognosis in the future," explains Zeng.
In addition, the researchers found that the inhibition of autophagy reduced the incidence of ovarian cancer cells driven by the PTP4A3 protein their experiments.
"This study suggests that autophagy could be used as a potential target for arresting PTP4A3-driven tumor progression in patients with high expression of both PTP4A3 and autophagy genes," says Zeng.