AZD8330 ARRY-424704 ole in liver carcino genesis Moreover recent

stuole in liver carcino genesis. Moreover, recent studies also showed that activation of Hedgehog signaling is critically re lated AZD8330 ARRY-424704 to CSCs and EMT features in many types of cancers including colon, gastric, esophagus, hepatic, and other cancers. BMI1 signaling pathway BMI1 is a part of the polycomb group genes that are highly conserved throughout evolution. BMI acts as an epigenetic chromatin modifier and is known for its contribution to embryonic and stem cell self renewal programs. It is frequently overex pressed in different cancer types and disruption of BMI1 signaling has been linked to the activation of the hedgehog pathway in some cancers, such as medul loblastoma. Furthermore, BMI1 upregula tion is associated with malignant transformation and acquisition of the malignant phenotype in HCC.
Aberrant BMI1 expression is reported in many CSC populations and it has been shown to have a critical role in maintaining and propagating the SP popula tion in liver cancer. BMI1 is also highly expressed in CD133 liver CSCs. The role of BMI1 in liver CSC maintenance is confirmed by ectopic expression of BMI1 in murine BMS-806 hepatic stem progenitor cells. In these cells, BMI1 and the Wnt ??catenin pathway regulate the self renewal of normal or cancer stem cells in liver. Furthermore, BMI1 knockdown in SP cells completely abolished the tumorigenicity of SP cells. Moreover, repression of targets of BMI1 plays a crucial role in the oncogenic transfor mation of hepatic stem progenitor cells.
In addition to these signaling pathways, signal transducer and activator of transcription 3, mainly activated by IL 6 and its related cytokine, and IL 22 has been shown to play key roles in acute phase response, a protection against liver injury, the pro motion of liver regeneration. Furthermore, hy peractive STAT3 signaling results in expansion of oval cell numbers and trigger wound healing, cell migra tion, and proliferation. This signaling pathway may take part an important role of mainte nance of CSCs. Stem cell signaling network Multiple studies have suggested that Wnt ??catenin, Notch, Hedgehog, FGF, and TGF ??BMP signaling network is implicated in the maintenance of tissue homeostasis by regulating self renewal of normal stem cells as well as prolifera tion or differentiation of progenitor cells.
Especially, it is well established that Wnt ??catenin and Hedgehog signaling pathways are critical for embryogenic development, as well as in the biology of CSCs and in the acquisition of EMT. Breakage of the signaling network for normal stem cells leads to the transformation to CSC. Alternatively, acquisition of self renewal potential in progenitor cells due to epi genetic change or genetic alteration of stem cell sig naling related genes gives rise to CSC. Detailed anal yses on the dysregulation of Wnt ??catenin, Notch, Hedgehog, FGF, and TGF ??BMP signaling pathways in CSCs derived from a various type of human tissues or organ should be systematically investigated to better unde AZD8330 ARRY-424704 chemical structure

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