Loss of Tumor Suppressing Genes Spurs Development of Squamous Cell Cancer

Investigators at Monash University (Melbourne, Australia) studied SCC of the skin in a mouse model. They reported in the November 15, 2011, issue of the journal Cancer Cell that they had identified the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC in mice. Targeting of Grhl3 by an oncogenic microRNA network that was dependent on miR-21 underpinned the development of SCC in humans. Deletion of Grhl3 in adult epidermis evoked loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC.

PTEN (phosphatase and tensin homolog), which is missing in 60% to 70% of metastatic cancers in humans, is the name of a phospholipid phosphatase protein, and gene that encodes it. The PTEN gene acts as a tumor suppressor gene thanks to the role of its protein product in regulation of the cycle of cell division, preventing cells from growing and dividing too rapidly.

“Virtually every SCC tumor we looked at had almost undetectable levels of this particular gene, so its absence is a very profound driver of these cancers,” said senior author Dr. Stephen M. Jane, professor of medicine at Monash University. “Our research indicates that drugs already in clinical trials for other cancers may actually be effective in treating SCC - they just need to be applied to skin or head and neck cancers. This means that a number of the usual hurdles in getting therapies to trial have already been cleared, so patients could be reaping the benefits of this research in under five years.”

“It is a similar case with prevention,” said Dr. Jane. “There are strategies by which we could increase the expression of this gene that will likely afford some protection from skin cancer, for example in the form of a supplement in sun-cream. The molecules that would increase this expression are very well validated, so there would be few barriers to applying them in clinical trials.”

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