In Cancer Cell this week, an international team of researchers reports that distinct neural stem cell populations can contribute to the development of disparate brain tumors in response to the proto-oncogene MYCN. The researchers transduced wild-type or mutationally stabilized murine N-mycT58A into neural stem cells from murine brain tissue. They found that while transplantation of N-myc wild-type neural stem cells was insufficient for tumor formation, "N-mycT58A cerebellar and brain stem [neural stem cells] generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain [neural stem cells] developed diffuse glioma." This suggests that there is a context-dependent transformation of neural stem cells in the presence of an oncogenic signal, the researchers add.
Also in Cancer Cell this week, researchers in the US and China report that S1PR1-STAT3 signaling is a crucial aspect of myeloid cell colonization for the formation of metastases. The up-regulation of S1PR1-STAT3 in tumor cells activates S1PR1-STAT3 in cells in premetastatic sites, leading to the formation of a premetastatic niche. "Targeting either S1PR1 or STAT3 in myeloid cells disrupts existing premetastatic niches," the team writes. "S1PR1-STAT3 pathway enables myeloid cells to intravasate, prime the distant organ microenvironment and mediate sustained proliferation and survival of their own and other stromal cells at future metastatic sites."
Finally in Cancer Cell this week, researchers at the University of Southern California report on the efficacy of DNA methylation screening to identify epigenetic events that drive the survival of cancer cells. Using experimental and bioinformatic approaches, the team surveyed the residual DNA methylation profiles in cancer cells with highly impaired DNA methyltransferases, and then classified the profiles according to their methylation status in both normal and tumor tissue. "We used gene expression meta-analysis to identify regions that are dependent on DNA methylation-mediated gene silencing," the authors write. "We further showed experimentally that these genes must be silenced by DNA methylation for cancer cell survival, suggesting these are key epigenetic events associated with tumorigenesis."