Organogenesis of thyroid gland is

dependent on specific transcription factors which are responsible for differentiation Aurora Kinase cancer of progenitor cells. Certain cell-specific transcription factors namely thyroid transcription factor (TTF) 1, TTF 2, Hhex factor, pax 8, fgfr-2, and Eya1 possess distinctive roles in thyroid development[10,16]. However, their combined expression through a controlled regulation is essential to carry out cellular differentiation and expression of thyroid specific genes. Mature thyroid cells display a number of markers of differentiation such as thyroglobulin (Tg), thyroid peroxidase (TPO), and thyroid stimulating hormone receptor. The origin of cancer cells in thyroid has been described in various literatures; however, it still maintains its avenue for debate. The basic concept of multistep carcinogenesis considers transformation of well differentiated thyroid cancer cells of follicular origin into undifferentiated cells through sequential events which occur during maturation of thyroid epithelial cells[6]. On the contrary, others propose that these well-differentiated follicular cells rarely proliferate and thus

carry limited accumulated mutations in the cells. Also, the genetic mutations that are seen in well-differentiated cancers are not evident in anaplastic cancers[17]. Some authors favor the notion of fetal carcinogenesis which postulates that thyroid CSCs originate from abnormal transformation of fetal cells: (1) fetal thyroid stem cells, the primitive cells that express onco-fetal

protein responsible for the origin of ATC; (2) Thyroblasts, which express fetal protein and Tg give rise to PTC; and (3) Prothyrocytes, which are differentiated cells responsible for FTC/follicular adenoma[8,18]. Once they follow aberrant pathways of malignant transformation, these cells lose their ability to differentiate further and become a potential source of CSCs. Another concept of CSC theory, which has been proposed previously, suggests that these cells originate either from stem cells, progenitor cells or from de-differentiated mature thyroid cells[19]. Because of a shorter lifespan of somatic cells, researchers Entinostat claim that stem cells or progenitor cells represent their most likely the source. Much evidence exists on the fact that cancer comprises of heterogeneous cells out of which only a sub-population with stem-cell like characteristics are tumorigenic[6,10,19]. However, the concept of CSC in the cellular origin for thyroid tumors, in particular, cannot be clearly demonstrated using this model. Because CSC are isolated at an advanced-stage of the tumor, these cells, though, capable of initiating new tumor formation, are not described for cellular-origin by some authors[20].