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Lab Notes: Skin Cancer Spread Tied to Gene

MedPageToday, 2012

Overexpression of a gene known as PHIP is associated with the development of distant metastases and worse survival in malignant melanoma, researchers reported in the Proceedings of the National Academy of Sciences .
This gene's product is pleckstrin homology domain-interacting protein, which is involved in postnatal growth but also appears to play a role -- previously undetermined -- in some cancers.
So a team of researchers led by Mohammed Kashani-Sabet, MD, at Sutter Pacific Medical Foundation in San Francisco, explored this in a murine model, where they found that mice with high levels of the protein died much more rapidly than those with low levels.
They then examined PHIP expression in a large cohort of patients with melanoma, and determined that poor prognostic signs, such as skin ulceration and metastatic growth, correlated with overexpression of the gene.
Further experiments suggested that PHIP contributes to the regulation of certain pathways involved in tumor invasion.
"Thus, PHIP may represent a rational therapeutic target against a range of different, lethal solid tumor types," the researchers wrote.
The way yeast cells respond to exposure to the selective serotonin reuptake inhibitor sertraline (Zoloft) may reveal a possible new target for treating depression beyond serotonin.
Ethan Perlstein, PhD, of Princeton University, and colleagues found that the drug accumulated in the membranes of budding yeast cells, causing a curvature of the internal membrane.
A similar accumulation has been seen in human cells but the clinical relevance in the human brain is still debated, the researchers noted in their paper in PLoS One .
The fact that yeast cells -- which do not contain serotonin -- responded to sertraline suggests that SSRIs have additional effects outside of regulating the neurotransmitter and possibly points to additional targets for new antidepressants.
"These drugs have multiple effects on various targets in the cell -- and one of the targets might be specific membranes themselves," they said.