Hence, Esg is a critical stem cell determinant that maintains stemness by repressing differentiation-promoting factors, such as Pdm1.
Further demonstrated is that the therapeutic potential is sustained in vivo by the accumulation, survival and long-term persistence exclusively at the level of secondary lymphoid organs of the transplanted NPCs, which, in turn, modulate the in situ increase of major stem cell fate determinants.
As self-renewal and differentiation of neural stem cells is predominantly regulated by a number of stem cell fate determinants such as Notch, Wnt, Hedgehog, PTEN (phosphatase and tensin homolog) and TLX (Drosophila tailless homolog), also named NR2E1, it is possible that deregulation of such genes may be responsible for the regulation of tumorigenesis in neural cancers.
Here the molecular determinants of stem cell homing have recently been determined to be largely dependent on a CXC motif chemokine, stromal-derived factor-1 (SDF-1 or CXCL12), and its receptor, CXCR4.
SOX2 research thus far has heavily emphasized its crucial role in stem cell maintenance, lineage fate determinant and a necessary factor to reprogram somatic cells back towards pluripotency [5, 9, 10].
Moreover, RNAi-mediated BRD4 silencing led to reduced expression of key determinants of stem cell identity (e.g., OCT4, PRDM14, and NANOG) in human and mouse ESCs, mimicking the effects of compound treatment.
DT+dox brains also showed an increase in Notch (Hes1, Hes5, Notch1, Jagged1) and the repression of BMP (Bmp2, Bmpr-Ia, Bmpr-Ib) activity signatures, with Bmpr-Ia and -Ib being key determinants for stem cell responses to BMPs (Panchision et al, 2001).
We conclude that plasticity of the cancer stem cell phenotype is an important determinant of the prognosis of tumors.
In summary, plasticity of the cancer stem cell phenotype is an important determinant of the effectiveness of therapy, and its possibility cannot be neglected to gain an accurate understanding of the treatment response of human tumors.
