Easing literliterature around the part of KLF4 in inhibiting EMT and/or driving MET in unique biological ature on the part of KLF4 in inhibiting EMT and/or driving MET in distinct biological contexts. As an illustration, in the colon epithelial cell line RKO, KLF4 upregulates the levels of contexts. For example, within the colon epithelial cell line RKO, KLF4 upregulates the levels of a variety of epithelial-specific keratins, for example KRT8 and KRT18 [76]. Similarly, in nasophavarious epithelial-specific keratins, which include KRT8 and KRT18 [76]. Similarly, in nasopharynryngeal carcinoma, KLF4 can transcriptionally activate E-cadherin and Teflubenzuron MedChemExpress minimize the motility geal carcinoma, KLF4 can transcriptionally activate E-cadherin and minimize the motility and and invasion of cells. This reduction is at the very least partly rescued by shRNA-mediated E-cadinvasion of cells. This reduction is at the least partly rescued by shRNA-mediated E-cadherin herin knockdown in KLF4-expressing cells, suggesting a functional function of E-cadherin in knockdown in KLF4-expressing cells, suggesting a functional role of E-cadherin in regulatregulating these traits [77]. The direct transcriptional activation of CDH1 (E-cadherin) by ing these traits [77]. The direct transcriptional activation of CDH1 (E-cadherin) by KLF4 KLF4 has also been noted in MCF10A cells [78]. Additional, the overexpression of KLF4 in has also been noted in MCF10A cells [78]. Additional, the overexpression of KLF4 in MDAMDA-MB-231 breast cancer cells restored E-cadherin levels, induced an epithelial morMB-231 breast cancer cells restored E-cadherin levels, induced an epithelial morphology, phology, and suppressed migration and invasion [78], comparable to earlier observations in and suppressed migration and invasion [78], equivalent to prior observations in these cells for a further MET-TF, GRHL2 [14]. Consistently, KLF4 overexpression decreased levels ofCancers 2021, 13,11 ofvimentin and Slug and increased those of E-cadherin in OVCAR3 ovarian cancer cells [79]. These observations are reminiscent from the impact of KLF4 knockdown within a prostate stem cell line exactly where the cells lost their epithelial markers, including E-cadherin, ZO-1, and cytokeratin eight, and showed elevated levels of vimentin, SNAIL, SLUG, and ZEB1 [80]. Supporting these in vitro observations, in pancreatic cancer samples, KLF4 correlated positively with E-cadherin and negatively with vimentin and Cav-1, a direct transcriptional target of KLF4 which will inhibit EMT in pancreatic cancer [81]. KLF4 can also promote stemness in various cancers exactly where it promotes epithelial differentiation, thereby challenging the tacitly assumed association amongst EMT and cancer stem cells (CSCs) [82]. In breast cancer, KLF4 knockdown decreased ALDH1+ CSCs and N-Nitrosomorpholine custom synthesis mammosphere formation in vitro in MCF7 and MDA-MB-231 cells [41]. In vivo tumorigenesis and metastasis were also compromised in KLF4-depleted NOD/SCID mice [41,83]. In hepatocellular carcinoma, KLF4 straight activated EpCAM, increased the number of EpCAM+ /CD133+ liver cancer stem cells in vitro, and amplified the tumorigenesis in vivo [84]. Similarly, in osteosarcoma cells, KLF4 suppression prevented sphere formation and attenuated the levels of lots of stem cell-related markers, including ALDH1A1 [85]. Conversely, KLF4-overexpressing cells were far more chemoresistant and metastatic [86], and osteosarcoma stem cells had enhanced levels of KLF4 [87]. Considered collectively, these observations recommend that KLF4 might associate with far more epithelial-like and.
