Recent findings provide evidence for a functional interplay between DNA replication and the seemingly distinct areas of cancer, development and pluripotency. Protein complexes participating in DNA replication origin licensing are now known to have roles in development, while their deregulation can lead to cancer. Moreover, transcription factors implicated in the maintenance of or reversal to the pluripotent state have links to the pre-replicative machinery. Several studies have shown that overexpression of these factors is associated to cancer.

Background/Aim: Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) are critically implicated in cancer metastasis and chemoresistance. Herein, we investigated integrin-linked kinase (ILK)'s role in human colon cancer (CRC) progression and chemoresistance in relation to EMT and CSC markers. Patients and Methods: Expression of ILK, EMT and CSC markers were evaluated by immunohistochemistry in 149 CRC samples. We also generated colon cancer cells resistant to 5-FU and oxaliplatin and studied the effect of ILK inhibition on drug response by MTT assay and on EMT and CSC markers' expression. Results: ILK expression in human CRC correlates with EMT and CSC markers and is associated with metastasis and chemoresistance. ILK inhibition increases sensitivity of resistant cells to 5-FU and oxaliplatin and reduces the levels of EMT and CSC markers in 5-FU resistant cells. Conclusion: ILK overexpression in human CRC associates with EMT and CSC traits, contributing to tumor progression and chemoresistance.

Type 1 diabetes results from an insufficiency of insulin production as a result of autoimmune destruction of the insulin-secreting pancreatic β-cells. It can be treated by transplantation of islets of Langerhans from human donors, but widespread application of this therapy is restricted by the scarcity of donor tissue. Generation of functional β-cells from embryonic stem (ES) cells in vitro could provide a source of an alternative graft material. Several ES cell differentiation protocols have reported the production of insulin-producing cells by mimicking the in vivo developmental stages of pancreatic organogenesis in which cells are transitioned through mesendoderm, definitive endoderm, foregut endoderm, pancreatic endoderm, and the endocrine precursor stage, until mature β-cells are obtained. These studies provide proof of concept that recapitulating pancreatic development in vitro offers a useful strategy for generating β-cells, but current differentiation protocols employ a bewildering variety of growth factors, mitogens, and pharmacological agents. In this review, we will attempt to clarify the functions of these agents in in vitro differentiation strategies by focusing on the intracellular signaling pathways through which they operate – phosphatidylinositol 3-kinase, transforming growth factor β, Wnt/β-catenin, Hedgehog, and Notch.