A transcriptional response to Wnt protein in human embryonic carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Wnt signaling is implicated in many developmental decisions, including stem cell control, as well as in cancer. There are relatively few target genes known of the Wnt pathway.</p> <p>Results</p> <p>We have identified target genes of Wnt signaling using microarray technology and human embryonic carcinoma cells stimulated with active Wnt protein. The ~50 genes upregulated early after Wnt addition include the previously known Wnt targets Cyclin D1, MYC, ID2 and βTRCP. The newly identified targets, which include MSX1, MSX2, Nucleophosmin, Follistatin, TLE/Groucho, Ubc4/5E2, CBP/P300, Frizzled and REST/NRSF, have important implications for understanding the roles of Wnts in development and cancer. The protein synthesis inhibitor cycloheximide blocks induction by Wnt, consistent with a requirement for newly synthesized β-catenin protein prior to target gene activation. The promoters of nearly all the target genes we identified have putative TCF binding sites, and we show that the TCF binding site is required for induction of Follistatin. Several of the target genes have a cooperative response to a combination of Wnt and BMP.</p> <p>Conclusions</p> <p>Wnt signaling activates genes that promote stem cell fate and inhibit cellular differentiation and regulates a remarkable number of genes involved in its own signaling system.</p

Role of mesenchymal cells in the natural history of ovarian cancer: a review

International audienceBackground: Ovarian cancer is the deadliest gynaecologic malignancy. Despite progresses in chemotherapy and ultra-radical surgeries, this locally metastatic disease presents a high rate of local recurrence advocating for the role of a peritoneal niche. For several years, it was believed that tumor initiation, progression and metastasis were merely due to the changes in the neoplastic cell population and the adjacent non-neoplastic tissues were regarded as bystanders. The importance of the tumor microenvironment and its cellular component emerged from studies on the histopathological sequence of changes at the interface between putative tumor cells and the surrounding non-neoplastic tissues during carcinogenesis. Method: In this review we aimed to describe the pro-tumoral crosstalk between ovarian cancer and mesenchymal stem cells. A PubMed search was performed for articles published pertaining to mesenchymal stem cells and specific to ovarian cancer. Results: Mesenchymal stem cells participate to an elaborate crosstalk through direct and paracrine interaction with ovarian cancer cells. They play a role at different stages of the disease: survival and peritoneal infiltration at early stage, proliferation in distant sites, chemoresistance and recurrence at later stage. Conclusion: The dialogue between ovarian and mesenchymal stem cells induces the constitution of a pro-tumoral mesencrine niche. Understanding the dynamics of such interaction in a clinical setting might propose new therapeutic strategies