Cancer-associated fibroblasts (CAFs) in the tumor stroma play a key role in tumor progression. Erdogan et al. show that CAF-mediated alignment of the fibronectin matrix is a key factor promoting directional cancer cell migration.

Cancer-associated fibroblasts (CAFs) are major components of the surrounding stroma of carcinomas that emerge in the tumor microenvironment as a result of signals derived from the cancer cells. Biochemical cross-talk between cancer cells and CAFs as well as mechanical remodeling of the stromal extracellular matrix (ECM) by CAFs are important contributors to tumor cell migration and invasion, which are critical for cancer progression from a primary tumor to metastatic disease. In this review, we discuss key paracrine signaling pathways between CAFs and cancer cells that promote cancer cell migration and invasion. In addition, we discuss physical changes that CAFs exert on the stromal ECM to facilitate migration and invasion of cancer cells.

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BackgroundAlthough advances in sequencing technologies have popularized the use of microRNA (miRNA) sequencing (miRNA-seq) for the quantification of miRNA expression, questions remain concerning the optimal methodologies for analysis and utilization of the data. The construction of a miRNA sequencing library selects RNA by length rather than type. However, as we have previously described, miRNAs represent only a subset of the species obtained by size selection. Consequently, the libraries obtained for miRNA sequencing also contain a variety of additional species of small RNAs. This study looks at the prevalence of these other species obtained from bone marrow aspirate specimens and explores the predictive value of these small RNAs in the determination of response to therapy in myelodysplastic syndromes (MDS).MethodsPaired pre and post treatment bone marrow aspirate specimens were obtained from patients with MDS who were treated with either azacytidine or decitabine (24 pre-treatment specimens, 23 post-treatment specimens) with 22 additional non-MDS control specimens. Total RNA was extracted from these specimens and submitted for next generation sequencing after an additional size exclusion step to enrich for small RNAs. The species of small RNAs were enumerated, single nucleotide variants (SNVs) identified, and finally the differential expression of tRNA-derived species (tDRs) in the specimens correlated with diseasestatus and response to therapy.ResultsUsing miRNA sequencing data generated from bone marrow aspirate samples of patients with known MDS (N = 47) and controls (N = 23), we demonstrated that transfer RNA (tRNA) fragments (specifically tRNA halves, tRHs) are one of the most common species of small RNA isolated from size selection. Using tRNA expression values extracted from miRNA sequencing data, we identified six tRNA fragments that are differentially expressed between MDS and normal samples. Using the elastic net method, we identified four tRNAs-derived small RNAs (tDRs) that together can explain 67 % of the variation in treatment response for MDS patients. Similar analysis of specifically mitochondrial tDRs (mt-tDRs) identified 13 mt-tDRs which distinguished disease status in the samples and a single mt-tDR which predited response. Finally, 14 SNVs within the tDRs were found in at least 20 % of the MDS samples and were not observed in any of the control specimens.DiscussionThis study highlights the prevalence of tDRs in RNA-seq studies focused on small RNAs. The potential etiologies of these species, both technical and biologic, are discussed as well as important challenges in the interpretation of tDR data.ConclusionsOur analysis results suggest that tRNA fragments can be accurately detected through miRNA sequencing data and that the expression of these species may be useful in the diagnosis of MDS and the prediction of response to therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1929-y) contains supplementary material, which is available to authori...

BackgroundThe conserved habenular nuclei function as a relay system connecting the forebrain with the brain stem. They play crucial roles in various cognitive behaviors by modulating cholinergic, dopaminergic and serotonergic activities. Despite the renewed interest in this conserved forebrain region because of its importance in regulating aversion and reward behaviors, the formation of the habenular nuclei during embryogenesis is poorly understood due to their small size and deep location in the brain, as well as the lack of known markers for habenular progenitors. In zebrafish, the bilateral habenular nuclei are subdivided into dorsal and ventral compartments, are particularly large and found on the dorsal surface of the brain, which facilitates the study of their development.ResultsHere we examine the expression of a homeodomain transcription factor, dbx1b, and its potential to serve as an early molecular marker of dorsal habenular progenitors. Detailed spatiotemporal expression profiles demonstrate that the expression domain of dbx1b correlates with the presumptive habenular region, and dbx1b-expressing cells are proliferative along the ventricle. A lineage-tracing experiment using the Cre-lox system confirms that all or almost all dorsal habenular neurons are derived from dbx1b-expressing cells. In addition, mutant analysis and pharmacological treatments demonstrate that both initiation and maintenance of dbx1b expression requires precise regulation by fibroblast growth factor (FGF) signaling.ConclusionsWe provide clear evidence in support of dbx1b marking the progenitor populations that give rise to the dorsal habenulae. In addition, the expression of dbx1b in the dorsal diencephalon is tightly controlled by FGF signaling.