Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

Figure 2

Common signaling pathways between Stem Cells (SCs) and Cancer Stem Cells (CSCs) [48]. CSCs share common signaling pathways, like the JAK/STAT, Hedgehog, Wnt, Notch, PTEN/AKT/P13K, NF-κB, MAPK/ERK, and SMAD. These SCs mechanisms are altered in CSCs and are characteristic of the cancer types mentioned. The JAK/STAT pathway (Janus kinase/signal transducer and activator of transcription) is mainly involved in glioblastoma development and breast CSCs [49–52]. The Hedgehog pathways have effects on the patterning of the embryo but play a crucial role in the induction of myelogenous leukemia. Blocking of the Hedgehog pathway decreases the quantity of CSCs in leukemia, then representing an important target for cancer therapy [53]. The Wnt pathway is an important regulator of SCs and CSCs regarding self-renewal, being perturbed in colon cancer and leukemia [54–56]. The Notch pathway is involved in the development of breast tissue as a regulator of cell fate and differentiation. An excess in the activation of Notch could determine the aggressiveness of breast cancer [55, 57–59]. The phosphatase and tensin homolog (PTEN)/protein kinase B (PKB or AKT)/phosphatidylinositide 3-kinase (P13K) signaling is a key regulator of self-renewal and maintenance of SCs and CSCs with an important role in the emergence of CSCs in prostate cancer [51, 60]. The NF-κB pathway is crucial for leukemic cells survival and its inhibition affects CSCs development in breast cancer [61]. It has been seen that the increase of neural stem cell (NSC) proliferation is caused by the activation of NF-κB, through the TNF-α signal transduction pathway, but its aberrant regulation could lead to CSCs development in glioblastomas [62, 63]. Blocking the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) results in the growth inhibition of breast cancer and the emergence of CSCs, sensitizing cancer cells to chemotherapy [64–66]. Gastrointestinal SCs can be perturbed, changing their plasticity and differentiation potential by generating an aberrant response to TGF-β affecting the SMAD pathway and generating CSCs [67]. The hepatocellular carcinoma is an aggressive form of cancer in which the TGF-β, Notch, and Wnt are deregulated, also having consequences in the SMAD proteins and changing SCs renewal, differentiation, and survival patterns [68, 69]. In adult and CSCs systems all the mentioned pathways are common and conserved in the control of SCs renewal, proliferation, and differentiation.