Plasticity and Tumorigenicity

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The research fields of developmental biology and oncology have always been tightly linked, since the times of Rudolf Virchow's cellular theory (>omnis cellula e cellula>) and embryonal rest hypothesis. On the other side, for many years, contemporary cancer research has been mainly focused on the altered controls of proliferation in tumoral cells. This has been reflected in the therapeutic approaches employed in the clinic to treat the patients: with very few exceptions, anti-cancer treatments are targeted at the mechanisms of abnormal tumoral growth. Such therapies, however, are very unspecific, highly toxic and, ultimately, inefficient in most cases. In the last years, a new recognition of the role of aberrant differentiation at the root of cancer has arisen, mainly driven by the coming of age of the >cancer stem cell> (CSC) theory. From this point of view, the comprehensive knowledge of the developmental mechanisms by which normal cells acquire their identity is essential to understand how these controls are deregulated in tumours. New insights into the mechanisms that maintain the molecular boundaries of cell identity have been gained from the study of induced pluripotency, showing that cell fate can be much more susceptible to change than previously thought. Applied to cancer, these findings imply that the oncogenic events that take place in an otherwise healthy cell lead to a reprogramming of the normal cellular fate and establish a new pathologic developmental program. Therefore, cancer reprogramming and cellular plasticity are closely related, since only some cells possess the plasticity required to allow reprogramming to occur, and only some oncogenic events can, in the right plastic cell, induce this change. Here we discuss the latest findings in the fields of cellular plasticity and reprogramming and we consider their consequences for our understanding of cancer development and treatment.
Research in C.C. lab was partially supported by FEDER, Fondo de Investigaciones Sanitarias (PI080164), CSIC P.I.E. 200920I055 and 201120E060, from the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program) and from an institutional grant from the "Fundación Ramón Areces". Research in ISG group was partially supported by FEDER and by MICINN (SAF2009- 08803 to ISG), by Junta de Castilla y León (REF. CSI007A11-2 and Proyecto Biomedicina 2009-2010), by MEC OncoBIO Consolider-Ingenio 2010 (Ref. CSD2007-0017), by NIH grant (R01 CA109335- 04A1), by Sandra Ibarra Foundation, by Group of Excellence Grant (GR15) from Junta de Castilla y Leon, and the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program) and by >Proyecto en Red de Investigación en Celulas Madre Tumorales en Cancer de Mama>, supported by Obra Social Kutxa y Conserjería de Sanidad de la Junta de Castilla y León. All Spanish funding is co-sponsored by the European Union FEDER program. ISG is an API lab of the EuroSyStem project. ECS is the recipient of a JAE-predoc Fellowship from CSIC and a "Residencia de Estudiantes" Fellowship. The authors declare no conflict of interest.