FGF Signaling Pathway: A Key Regulator of Stem Cell Pluripotency

Mossahebi-Mohammadi, Majid; Quan, Mei‐Yu; Zhang, Jin‐San; Li, Xiaokun

doi:10.3389/fcell.2020.00079

Cited by 168 publications

(119 citation statements)

References 104 publications

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“…3-5). PI3K/Akt/GSK-3β is a well-known classical pathway to regulate both cell proliferation and apoptosis [51][52][53] . In our RNA-seq results, the DEGs were also enriched in PI3K/Akt pathway by knocking out IL-17 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

et al. 2020

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We aimed to investigate the exact effect of IL-17 on regulating neural stem cells (NSCs) stemness and adult neurogenesis in ischemic cortex after stroke, how Astragaloside IV(As-IV) regulated IL-17 expression and the underlying mechanism. Photochemical brain ischemia model was established and IL-17 protein expression was observed at different time after stroke in WT mice. At 3 days after stroke, when IL-17 expression peaked, IL-17 knock out (KO) mice were used to observe cell proliferation and neurogenesis in ischemic cortex. Then, As-IV was administered intravenously to assess cell apoptosis, proliferation, neurogenesis, and cognitive deficits by immunochemistry staining, western blots, and animal behavior tests in WT mice. Furthermore, IL-17 KO mice and As-IV were used simultaneously to evaluate the mechanism of cell apoptosis and proliferation after stroke in vivo. Besides, in vitro, As-IV and recombinant mouse IL-17A was administered, respectively, into NSCs culture, and then their diameters, viable cell proliferation and pathway relevant protein was assessed. The results showed knocking out IL-17 contributed to regulating PI3K/Akt pathway, promoting NSCs proliferation, and neurogenesis after ischemic stroke. Moreover, As-IV treatment helped inhibit neural apoptosis, promote the neurogenesis and eventually relieve mice anxiety after stroke. Unsurprisingly, IL-17 protein expression could be downregulated by As-IV in vivo and in vitro and they exerted antagonistic effect on neurogenesis by regulating Akt/GSK-3β pathway, with significant regulation for apoptosis. In conclusion, IL-17 exerts negative effect on promoting NSCs proliferation, neurogenesis and cognitive deficits after ischemic stroke, which could be reversed by As-IV.

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Section: Discussionmentioning

confidence: 99%

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

et al. 2020

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“…Along with the ERBB-family of RTKs, MEMO1 was also found to interact with the Fibroblast Growth Factor Receptor (FGFR) family ( Figure 1B). FGF signaling has important roles in several cellular and physiological events in both the embryonic and adult organism [14]. Similar to HRG, upon Fibroblast Growth Factor 2 (FGF2) stimulation, cellular motility-of a breast cancer cell line-was reduced after siRNA-mediated knockdown of MEMO1, relative to controls [1].…”

Section: Part Imentioning

confidence: 99%

Finding MEMO—Emerging Evidence for MEMO1′s Function in Development and Disease

Schotanus

Otterloo

2020

Genes

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Although conserved throughout animal kingdoms, the protein encoded by the gene Mediator of ERBB2 Driven Cell Motility 1 or MEMO1, has only recently come into focus. True to its namesake, MEMO1 first emerged from a proteomic screen of molecules bound to the ERBB2 receptor and was found to be necessary for efficient cell migration upon receptor activation. While initially placed within the context of breast cancer metastasis—a pathological state that has provided tremendous insight into MEMO1′s cellular roles—MEMO1′s function has since expanded to encompass additional cancer cell types, developmental processes during embryogenesis and homeostatic regulation of adult organ systems. Owing to MEMO1′s deep conservation, a variety of model organisms have been amenable to uncovering biological facets of this multipurpose protein; facets ranging from the cellular (e.g., receptor signaling, cytoskeletal regulation, redox flux) to the organismal (e.g., mineralization and mineral homeostasis, neuro/gliogenesis, vasculogenesis) level. Although these facets emerge at the intersection of numerous biological and human disease processes, how and if they are interconnected remains to be resolved. Here, we review our current understanding of this ‘enigmatic’ molecule, its role in development and disease and open questions emerging from these previous studies.

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“…Additionally, FGF appears to be an indispensable supplementary growth factor in the cancer stemness-inducing (CSI) medium, and FGF2 in particular has been widely used to trigger spheroid formation in vitro. Despite the strong evidence suggesting that FGF/FGFR signal is indeed an essential factor in governing cancer stemness and a potential target for cancer therapy (Touat et al, 2015;Hallinan et al, 2016;Mossahebi-Mohammadi et al, 2020), the underlying mechanisms of how FGF/FGFR regulates cancer stemness are still unknown.…”

Section: Introductionmentioning

confidence: 99%

An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness

Quan

Guo

Liu

et al. 2020

Front. Cell Dev. Biol.

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Cancer stemness is associated with high malignancy and low differentiation, as well as therapeutic resistance of tumors including pancreatic ductal adenocarcinoma (PDAC). Fibroblast growth factors (FGFs) exert pleiotropic effects on a variety of cellular processes and functions including embryonic stem cell pluripotency and cancer cell stemness via the activation of four tyrosine kinase FGF receptors (FGFRs). FGF ligands have been a major component of the cocktail of growth factors contained in the cancer stemness-inducing (CSI) and organoid culture medium. Although FGF/FGFR signaling has been hypothesized to maintain cancer stemness, its function in this process is still unclear. We report that inhibition of FGF/FGFR signaling impairs sphereforming ability of PDAC in vitro, and knocking down FGFR1 and FGFR2 decreased their tumorigenesis abilities in vivo. Mechanistically, we demonstrated that SOX2 is down-regulated upon loss of FGFR signaling. The overexpression of SOX2 in SOX2negative cells, which normally do not display stemness capabilities, is sufficient to induce spheroid formation. Additionally, we found that AKT phosphorylation was reduced upon FGFR signaling inhibition. The inhibition of AKT using specific pharmacological inhibitors in the context of CSI medium leads to the loss of spheroid formation associated with loss of SOX2 nuclear expression and increased degradation. We demonstrate that an FGFR/AKT/SOX2 axis controls cancer stemness in PDAC and therefore may represent an important therapeutic target in the fight against this very aggressive form of cancer.

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FGF Signaling Pathway: A Key Regulator of Stem Cell Pluripotency

Cited by 168 publications

References 104 publications

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

Finding MEMO—Emerging Evidence for MEMO1′s Function in Development and Disease

An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness

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