CSCs are also associated with chemoresistance, relapse, and metastasis [156]. Mani et al. reported that EMT could induce stem-like Transmembrane Transporters inhibitor properties in non-cancerous mammary epithelial cells [14]. The CD44high/CD24low phenotype correlates with both breast CSCs and normal mammary stem cells, and both Snail1- and Twist-induced EMTs stimulated this same phenotype in nontumorigenic human mammary epithelial cells (HMLEs). These EMTs also increased the HMLEs’ mammosphere-forming ability thirty-fold, and the CD44high/CD24low cells are able to produce

more CD44high/CD24low cells in addition to CD44low/CD24high cells. Furthermore, these CD44high/CD24low cells exhibited a decrease of E-cadherin expression along with elevated

fibronectin, vimentin, Snail1, and Twist, as measured by RT-PCR [14]. Thus, EMT promotes self-renewal capabilities and the stem-like phenotype. Given that Snail1 induced EMT and a stem-like phenotype in human colorectal cancer cells (as mentioned in “Colorectal Carcinoma,” above), Zhou et al. examined human pancreatic cancer cells and reached similar conclusions [15]. Epithelial BxPC-3 cells were compared with more morphologically diverse Panc-1 cells, and the comparison identified Panc-1 cells, which had higher Snail1 expression and were more poorly differentiated than BxPC-3 cells, as CSChigh with a larger ALDHhigh population [15]. Stem cells’ pluripotent capabilities are maintained in part by the polycomb complex protein BMI-1 (Bmi-1), homeobox protein AZD6738 chemical structure Nanog, sex-determining region Y-box 2 (Sox2), and octamer-binding transcription factor 4 (Oct4) [157–159]. Snail1 silencing resulted in a decrease in ALDH, Sox-2, Oct-4, and invasive properties. Following Snail1 knockdown, E-cadherin expression increased as vimentin and ZEB1 expressions both decreased. Without Snail1, the Panc-1 cells underwent MET and consequently

lost their stem-like phenotype [15]. In a similar study of non-small cell lung cancer, Wang et al. compared ciplatin-resistant A549 cells with their A549 counterparts [16]. A549/CDDP cells showed increased expression levels of Nanog, Oct4, and Bmi-1, as detected by Western blot. RT-PCR also showed increased CD44 and Sox2. Migratory and invasive capacities were increased in A549/CDDP cells, as selleck inhibitor well. Interestingly, only Snail1 expression was elevated in A549/CDDP cells—Slug, Twist, and ZEB1 were not influential factors in this comparison. Snail1 knockdown again caused a decline in migration, invasiveness, Bmi-1 expression, Oct-4 expression, and mammosphere-forming ability. E-cadherin increased as vimentin BMS202 concentration decreased, and the cells became more responsive to cisplatin [16]. Since β-catenin had effects on the system comparable to active Snail1, an antagonist of the PI3K/Akt pathway was introduced, and this resulted in a decrease in β-catenin, Snail1, Nanog, migration, invasiveness, and mammosphere-forming ability [16].