The author of 《Intracellular Notch1 Signaling in Cancer-Associated Fibroblasts Dictates the Plasticity and Stemness of Melanoma Stem/Initiating Cells》 were Du, Yan; Shao, Hongwei; Moller, Mecker; Prokupets, Rochelle; Tse, Yee Ting; Liu, Zhao-Jun. And the article was published in Stem Cells (Durham, NC, United States) in 2019. Product Details of 106685-40-9 The author mentioned the following in the article:
Cancer stem cells (CSCs) play critical roles in cancer initiation, metastasis, recurrence, and drug resistance. Recent studies have revealed involvement of cancer-associated fibroblasts (CAFs) in regulating CSCs. However, the intracellular mol. mechanisms that determine the regulatory role of CAFs in modulating the plasticity of CSCs remain unknown. Here, we uncovered that intracellular Notch1 signaling in CAFs serves as a mol. switch, which modulates tumor heterogeneity and aggressiveness by inversely controlling stromal regulation of the plasticity and stemness of CSCs. Using mesenchymal stem cell-derived fibroblasts (MSC-DF) harboring reciprocal loss-of-function and gain-of-function Notch1 signaling, we found that MSC-DFNotch1-/- prompted cocultured melanoma cells to form more spheroids and acquire the phenotype (CD271+ and Nestin+) of melanoma stem/initiating cells (MICs), whereas MSC-DFN1IC+/+ suppressed melanoma cell sphere formation and mitigated properties of MICs. Our data demonstrate that intracellular Notch1 signaling in CAFs is a mol. switch dictating the plasticity and stemness of MICs, thereby regulating melanoma aggressiveness, and therefore that targeting the intracellular Notch1 signaling pathway in CAFs may present a new therapeutic strategy for melanoma. The amounts of CD271+ MIC regulated by MSC-DF carrying high or low Notch1 pathway activity is well correlated with capability of melanoma metastasis, supporting that melanoma metastasis is MIC-mediated. Consistently, when cografted with melanoma cells into NOD scid gamma (NSG) mice, MSC-DFNotch1-/- increased, but MSC-DFN1IC+/+ decreased, the amounts of CD271+ MIC in melanoma tissue. MSC-DFNotch1-/- increased stemness of CD271+ MIC, which resultantly exhibited stronger aggressiveness in vitro and in vivo, by upregulating Sox2/Oct4/Nanog expression. In the part of experimental materials, we found many familiar compounds, such as 6-(3-(Adamantan-1-yl)-4-methoxyphenyl)-2-naphthoic acid(cas: 106685-40-9Product Details of 106685-40-9)
6-(3-(Adamantan-1-yl)-4-methoxyphenyl)-2-naphthoic acid(cas:106685-40-9) is a third-generation synthetic retinoid and a highly lipophilic compound derived from naphthoic acid. It is widely used in the treatment of acne.Product Details of 106685-40-9
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