Stem Cells in Cancer and Aging Laboratory

Molecular Oncology
Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS)

In the traditional view of cell identity, terminally differentiated cells were highly specialized imperturbable entities. This notion was challenged half a century ago by the seminal work of John B. Gurdon using somatic cell nuclear transfer in Xenopus. Currently, we know that the nucleus of normal somatic cells can be reprogrammed to an induced-pluripotent stem cell (iPSC) stage, as reported by Shinya Yamanaka, using four transcription factors; namely Oct-4, Sox2, Klf4, and c-Myc. On the other hand, oncogenic transformation frequently involves de novo acquisition of developmental programs, similarly to what occurs during reprogramming to iPSCs. Furthermore, poorly differentiated aggressive tumours have been reported to express genetic programs that are closer to those present in embryonic stem cells. This similarity between oncogenic transformation and reprogramming to iPSCs is further reinforced at a mechanistic level, with common genes and programs enhancing or blocking both processes.

Although initially described in mouse and human fibroblasts, nowadays reprogramming to iPSC has been achieved using a variety of differentiated cell types from diverse species. A notable exception however, is the case of cancer cells with only sporadic examples of reprogramming of cell lines of mouse and human origin, and with very limited information derived from these attempts. As stated above, reprogramming to iPS cell and oncogenic transformation share many conceptual similarities and mechanistic pathways. The generation of iPSCs from cancer cells could illuminate molecular mechanisms underlying the pathogenesis of cancer, and deciphering the barriers underlying the reprogramming process of cancer cells could reveal information on the links between pluripotency and oncogenic transformation that would be instrumental for therapy development.

Molecular Biomedicine
Manuel Collado