Guest post by Kevin Measor
Prosaposin or PSAP, a glycoprotein encoded by the PSAP gene, can be cleaved into four products: saposins A, B, C, and D. All four are important for the hydrolysis of sphingolipids ― compounds known to play an important role in signal transmission and cell recognition. Mutations in the PSAP gene can lead to a host of diseases including Gaucher disease (a lysosomal storage disease) and Tay-Sachs disease, a devastating condition that usually results in death by early childhood .
Prosaposin is crucially affected during and following cerebral ischemia, where insufficient blood flow in the brain disrupts its processing and thus glycosphingolipid metabolism. This malfunction adversely affects synapses and cell signaling, and consequently normal brain function . Correspondingly, the precursor molecule has been shown to possess neuroprotective effects and can act as an important growth factor, either being secreted or presented as an integral membrane protein. A study in the Journal of Neurochemistry found that prosaposin, when secreted by stromal cell-derived neuroprogenitor cells in the bone marrow, can protect adult neural cells from apoptotic cell death .
More recently the role of prosaposin in cell signaling has been highlighted in cancer research. The anti-apoptotic protection offered by prosaposin has associated this pleiotropic growth factor with the promotion of proliferation of certain cancers. A recent study in the journal Cancer Science, has implicated PSAP expression in the promotion of breast cancer. The authors of this paper used Proteintech’s anti-PSAP antibody in an enzyme linked immunosorbent assay (ELISA) to detect prosaposin secreted into the cell culture media. The assay detected decreased levels of prosaposin in cells transfected with plasmid designed to knock down PSAP expression . The researchers in the Cancer Science study were able to show that prosaposin affects estrogen alpha-signaling in both in vivo and in vitro models of breast cancer. Decreased PSAP expression consequently led to a decrease in estrogen receptor alpha (ERa) expression and, accordingly, overexpression of this gene led to increased ERα levels.
The estrogen receptor plays an important role in estrogen hormone signaling ― a pathway that, when defective, contributes to the progression of certain kinds of estrogen-dependent breast cancers. The findings of the Cancer Science study support the theory that activation of this receptor can be achieved independently of estrogen, with the help of growth factors like prosaposin . In light of other findings that increased levels of prosaposin are associated with more aggressive forms of prostate cancer , such results suggest that prosaposin may be an important molecule in the protection of cancer cells, enabling them to survive and proliferate. Such work also presents prosaposin as a potential drug target in the development of stratified treatments for personalized cancer therapies.
Guest Blogger Profile
Kevin Measor is a PhD candidate in Neuroscience at the University of California, Riverside and an aspiring science writer. He studies how the auditory cortex of the bat processes different properties of sound. He also holds bachelors degrees in biology and history, and masters degrees in biology and education. In his spare time he enjoys hanging out with his infant son, reading and birding.
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