Table 1.

The differences among the cancer cells, cancer stem cells, and normal stem cells in the signaling pathways.

Signal pathway	Normal stem cells	Cancer and cancer stem cells
Polycomb-group protein family (Bmi-1)	➢Self-renewal in both hematopoietic and neural stem cells [154]	➢Leukemic stem cells (LSCs) self- renewal by suppression of the Ink4a/AR Flocus [155]. ➢Highly expressed in acute myeloid leukemia patients [156,157] as it is essential for the LSC self-renewal.
Notch	➢Neural stem cell expansion regulation in vivo and in vitro [158]. ➢Notch targets genes activation, which is involved in T-cell differentiation and self-renewal [159].	➢Notch signaling pathway mutations result in T-cell acute lymphopblastic leukemia (T-ALL) [122].
Wnt/β-catenin	➢Self-renewal [160]. ➢HoxB4 and Notch-1 gene activation, which is implicated in the self-renewal of Hematopoietic stem cells (HSC)s [151].	➢Colon carcinoma and blood diseases ➢β-catenin accumulation has been associated with breast or brain cancer, melanoma, and myeloid leukemia [162]. ➢β-catenin mutations observed in hepato-cellular, endometrial, and prostate carcinomas [162].
PTEN	➢Hematopoietic stem cells and neural stem cells maintenance	➢Loss of expression of Pten in mice results in aberrant self-renewal of HSCs and eventually leukemia [163]. ➢Loss of Pten eventually leads to myelo-proliferative disease and the emergence of a transplantable leukemia. ➢Mutations and/or loss of heterogeneity of Pten can cause glioblastoma, prostate, and endometrial carcinoma [164].
Sonic hedgehog (Shh)	➢Bmi-1 activation in the brain [165]. ➢The Shh signaling pathway is essential for the embryonic development of hair follicles and sebaceous glands [166]. ➢Shh signaling pathway is implicated in postnatal and adult brain development [167].	➢Shh activation leads to both skin and brain carcinogenesis [168]. ➢Shh mutation leads toGorlin’s syndrome [168].
Hox family	➢HSCs self-renewal [169].	➢Overexpressed in T-ALL with chromosome translocations [159]. ➢Hoxb 3, 8, and 10 are associated with leukemo-genesis in mice [169]. ➢HoxA9 is over-expressed in AML patients [169].