Cancers originate preferentially in adult tissue stem cells. Mus musculus

Stem cells have long been regarded as a potential origin of cancer. But cancers could also arise from mutated, differentiated cells that reacquire stem cell properties. Here, in mice harboring conditional oncogenic and lineage tracing alleles, we show that cancers develop from Prom1+ (CD133) cells, only in organs where these cells operate as stem cells. Allograft assays demonstrated that these cancers are not necessarily propagated by Prom1+ cancer stem cells, even when initiated in Prom1-lineages that maintain the normal organ. Normal and transformed Prom1+ stem cells in our mice, maintained the gastric mucosa and gastric adenocarcinomas, respectively. Comparison of these cells identified the latent sodium channel gene Nalcn as a novel gastric cancer suppressor that regulates the differentiation of stomach stem cell daughters. Our data provide new evidence that cancers are initiated preferentially within stem cells, and important insights into how these cells are deregulated to initiate and maintain cancers Overall design: Prom1 conditional mutants in mice that develped tumors and normal from cells various tissues in mice are compared. 117 samples were studied.