In Cancer Discovery this week, a team led by researchers at the University of California, San Francisco, reports that repression of CD36 activates a multicellular stromal program in tissues with high mammographic density and in tumor tissues. CD36 is a transmembrane receptor that regulates multiple pro-tumorigenic phenotypes like adipocyte differentiation and angiogenesis, the team says. In this study, the researchers found that CD36 is highly repressed in multiple disease-free stromal cell types associated with both high mammographic density and tumor tissue. "Using both in vitro and in vivo assays, we demonstrate that CD36 repression is necessary and sufficient to recapitulate the above-mentioned phenotypes observed in high [mammographic density] and tumor tissues," the authors write. "Consistent with a functional role for this coordinated program in tumorigenesis, we observe that clinical outcomes are strongly associated with CD36 expression."
Also in Cancer Discovery, researchers at the University of Virginia report that the proliferation of prostate cancer cells is regulated by a chimeric SLC45A3-ELK4 RNA generated by cis-splicing of the adjacent genes. The fusion of SLC45A3 and ELK4 plays an important role in both androgen-dependent and -independent prostate cancer cells, the researchers say. "The level of the chimeric transcript correlates with disease progression, with the highest levels in prostate cancer metastases," they add. "Our results suggest that gene fusions can arise from cis-splicing of adjacent genes without corresponding DNA changes.
Finally in Cancer Discovery, researchers in Massachusetts and California report that cancer-stimulated mesenchymal stem cells can create a carcinoma stem-cell niche through the prostaglandin E2 signaling pathway. The team found that carcinoma cell-derived interleukin-1 induces secretion of prostaglandin E2 by the mesenchymal stem cells and that the resulting prostaglandin E2 works with ongoing paracrine IL-1 signaling "to induce expression of a group of cytokines by the MSCs." The prostaglandin E2 and resulting cytokines then act in a paracrine fashion on the carcinoma cells "to induce activation of β-catenin signaling and formation of cancer stem cells," the authors add.