Cancer, a leading threat to human health, is unregulated cell growth characterized by genome instability. High mutation rates and irregularities in chromosomal structure can result in the evolution and competition of genetically distinct populations within a tumor. Termed intratumor heterogeneity (ITH), this diversity is linked to cell acquired therapy resistance and is thus currently critical for prognosis and therefore early diagnosis and treatment. Here, I describe Tasmanian devils (Sarcophilus harrisii) as a model for ITH and identify a gene, RASL11A, which has a homologue in humans that has been previously described as a putative tumor suppressor colorectal and prostate cancers. Devils are threatened due to the spread of a transmissible cancer, Devil facial tumor disease (DFTD). DFTD is fatal except in rare instances of spontaneous regression associated with activation of RASL11A. Here we provide evidence that expressing RASL11A in co-culture in vitro with wildtype cells whereby RASL11A over-expressed cell lines outgrow and outcompete wild-type DFTD lines. Determined “winners” in cellular competition, these findings highlight a potential role for RASL11A as a candidate for therapeutic investigation for human colorectal and prostate cancer.
Ciarra Polsley (Fri,) studied this question.