Melanoma Protein Stimulates Cancer Spread

Cancer researchers working on melanoma have learned that a protein called Mcl-1, which is mutated and over expressed in several types of cancers, acts to prevent unattached cells from undergoing the anoikis form of programmed cell death. Anoikis resistant cells have the potential to metastasize and spread the cancer to other sites in the body.

Mcl-1 is a member of the Bcl-2 protein family, several of which are up regulated in melanoma. In the current study investigators at Thomas Jefferson University (Philadelphia, PA, USA) used RNA interference to deplete Mcl-1 from melanoma cells growing in tissue culture. They reported in the April 2009 issue of the journal Molecular Cancer Research that the treated cells lost their resistance to anoikis, a form of apoptosis that kills cells when they become detached from the extracellular matrix. Depletion of other Bcl-2 proteins was much less effective than removal of Mcl-1.

"When we depleted Mcl-1 from the tumor cells, they were susceptible to cell death," said senior author Dr. Andrew Aplin, associate professor of cancer biology at Thomas Jefferson University. "Mcl-1 showed dramatic results compared to Bcl-2 and Bcl-XL, which was a surprise. Our findings show that targeting Mcl-1, which is up regulated in a majority of melanoma cells, could be a viable treatment strategy."

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