The stem cell-like phenotype of various cancer type is directly correlated with increased malignancy as well as with resistance to conventional and targeted therapies. Number of tumour type and subtypes can be distinguished by various features of plutipotency. It is also postulated and supported by increasing evidence that oncogenesis resembles the process of cellular reprogramming. Importantly, the cocktail of 4 reprogramming factors is composed of 2 well-known proto-oncogenes, c-Myc and Klf4 which further connects induced pluripotency and oncogenesis. The multiple similarities between pluripotent cells and cancer cells have led to widespread interest of researchers to discover molecular mechanisms that link these two cell types. Indeed, the stem cells and cancer cells share certain common characteristics, such as ability to self-renew and block in differentiation. Both cell types have a rapid cell cycle and high telomerase activity that result in uncontrolled proliferation. The stem cell-like phenotype can be also linked with other Pan-Cancer Themes already proposed in our group, including Notch pathway, TP53-mediated damage response PI3K pathway, Ras/MAPK pathway, Wnt/beta-catenin signalling, and TERT.
What are the goals of this project?
The aim is to investigate The PanCanAtlas Stemness/De-differentiation group will perform characterisations of the stem-cell like phenotype. This will include: (1) expression of pluripotency markers: Nanog, Oct4, Sox2, Kit, Klf4, Lefty1, and others; (2) mutations, amplification in genes involved in pluripotency, (3) deletions, methylation of genes and their promoters responsible for methylation; (4) expression of miRNAs expressed in stem cells and repression of these responsible for differentiation; (5) expression and activation of proteins engaged in pathways regulating stemness. The molecular profile will be also linked to the markers of EMT.
What is the impact of this project?
Having made this characterisations, we will be in a unique position to perform a ranged of the correlations/associations studies with results of value to the field of cancer biology and therapy.
The Children's Brain Tumor Network contributed to this project by providing access to the Pediatric Brain Tumor Atlas.
PI: Maciej Wiznerowicz, International Institute for Molecular Oncology
Sylwia Mazurek, Bioinformatician
Adam Resnick, PhD
Adam Resnick is the Director of Data Driven Discovery in Biomedicine (D3b) at Children’s Hospital of Philadelphia (CHOP) responsible for leading a multidisciplinary team to build and support a scalable, patient-focused healthcare and educational discovery ecosystem on behalf of all children. He i
Children’s Hospital of Philadelphia