In Cancer Research this week, researchers in the US and Canada present their findings on the difference in differentiation between estrogen receptor α-positive and α-negative breast cancers. "In this study, we identify ... coactivator-associated arginine methyltransferase 1, a unique coactivator of ERα that can simultaneously block cell proliferation and induce differentiation through global regulation of ERα-regulated genes," the authors write. The team suggests that coexpression of CARM1 and ERα may be a biomarker of well-differentiated breast cancer.
Also in Cancer Research this week, researchers in Japan present a study on the interactions between CCL11 and CCR3 that promote survival of anaplastic large cell lymphoma cells. The team investigated the role of CCL11 in cell survival and growth of human Ki-JK cells, which express cell surface CCR3. "CCL11 increased cell survival rates of Ki-JK cells in a dose-dependent manner," the team writes. "Furthermore, CCL11 induced phosphorylation of extracellular signal-regulated kinase 1/2 in both Ki-JK cells and EL-4 cells. Cell survival and tumor proliferation promoted by CCL11 was completely blocked by inhibition of ERK phosphorylation." These findings could lead to a novel therapeutic approach to treating this aggressive form of lymphoma, the authors add.
Researchers in the UK say genome-wide analysis of alternative splicing in medulloblastoma identifies splicing patterns characteristic of normal cerebellar development. The pattern of differential splicing in three of the team's validated events was characteristic for the molecular subset of sonic hedgehog-driven medulloblastomas, indicating that their gene signature includes the expression of distinctive transcript variants, the researchers write. "We investigated whether tumor-associated splice forms were expressed in primary cultures of Shh-dependent mouse cerebellar granule cell precursors and found that Shh caused a decrease in the cassette exon inclusion rate of five of the seven tested genes," they add. "We conclude that inappropriate splicing frequently occurs in human medulloblastomas and may be linked to the activation of developmental signaling pathways and a failure of cerebellar precursor cells to differentiate."
And finally in Cancer Research this week, researchers in Michigan have identified a tumor suppressor relay between the FOXP3 and the HIPPO pathways in breast and prostate cancers. Spontaneous mutation of the transcription factor FOXP3 reduces expression of the LATS2 gene in mammary epithelial cells, the team writes, adding, "LATS2 induction required binding of FOXP3 to a specific sequence in the LATS2 promoter, and this interaction contributed to FOXP3-mediated growth inhibition of tumor cells." These findings suggest a novel mechanism of LATS2 downregulation in cancer, the researchers write.