Development Undone: Cellular Plasticity in Cancer

Abstract

Many cancers manifest stem cell-like characteristics; the acquisition of which is associated with tumour formation, drug resistance and metastasis. Unlike normal stem cells, which sustain a balance of self-renewal and differentiation, cancer cells favour the aberrant maintenance of self-renewal promoting factors. Using developmental model systems we have discovered that cancer cells express several stem cell associated factors. Of particular interest is Nodal, an embryonic morphogen that sustains the pluripotency of human embryonic stem cells (hESCs). Nodal signalling promotes tumour growth, invasion and angiogenesis in melanoma and breast cancer model systems. Ongoing studies are determining the mechanisms by which Nodal affects these tumourigenic processes. Most recently, we have begun to examine how biophysical factors, such as decreased oxygen levels (hypoxia) affect cell fate in cancer cells and in hESCs. Our work has shown that hypoxia supports cellular plasticity and pluripotency in cancer and hESCs, respectively. By understanding how the microenvironment affects cell fate, we hope to uncover therapeutic modalities designed to predict and eradicate aggressive cancers.