Independent of its transcriptional targets, thus providing yet a different potential mechanism for c-Myc induced genomic instability. Recent findings that tumorigenic cells can comprise a significant fraction of the tumor mass question the strictly hierarchical organization of the tumor tissue, and rather argue for ”phenotypic plasticity” of tumor cells, maintained by homeostatic mechanisms. Hence, CSCs do not exist as a unique population defined by discrete molecular properties, but rather together with their differentiated progeny constitute a selfreproducing ”stem cell system” where the cellular composition is regulated by interconversion of various differentiation states. Tumors of epithelial origin usually display high histological heterogeneity reflecting various differentiation states of individual cells. Based on three phenotypic criteria – cell polarization, cell cohesiveness and expression pattern of cytoplasmic intermediate filament proteins – it has been suggested to define four phenotypes, ranging from purely epithelial to entirely mesenchymal. Accordingly, the differentiation state of individual cells in carcinomas corresponds to an epithelial, a mesenchymal and an intermediate phenotype. These differentiation states can be further subdivided into stable and transitory subtypes, which altogether are assembled into a dynamic ”ecosystem”. The process termed epithelial-mesenchymal transition and its counterpart, termed mesenchymal-epithelial transition, describe the conversion of opposite differentiation states. These transitions have been recently linked to cell stemness by the observation that induction of EMT in human breast epithelial cell culture models creates a subset of cells highly enriched in CSCs. The model emerging from these studies proposes that in carcinomas EMT and MET account for the generation of a subset of cells which are in balance with the tumor epithelial compartment and are able to regenerate the whole tumor cell population. This new c-Myc function was demonstrated by its ability to bind to components of the prereplication complex, both in mammalian as well as in Cycloheximide Xenopus cells, and to influence the rate of DNA replication in Xenopus cell-free extracts. In addition, c-Myc binds to known mammalian replication origins. We hypothesized that overexpression of cMyc might accelerate S-phase, leading to increased sensitivity to replication stress. These results are consistent with work on the larvae of several other lepidopteran species, in which a melanic phenotype is produced as a plastic response to the environment. In these studies, as well as those conducted on the bl mutant, topical treatment of melanic individuals with JH or a JH analog rescued the lighter phenotype in subsequent larval instars. Furthermore, studies in M. sexta revealed that reduction of JH led to a two-fold increase in dopa decarboxylase.