Aurora-A-mediated phosphorylation of LKB1 compromises LKB1/AMPK signaling axis to facilitate NSCLC growth and migration

Oncogene ◽  
2017 ◽  
Vol 37 (4) ◽  
pp. 502-511 ◽  
Author(s):  
X Zheng ◽  
J Chi ◽  
J Zhi ◽  
H Zhang ◽  
D Yue ◽  
...  
Keyword(s):  
Aurora A ◽  
Ampk Signaling ◽  
Signaling Axis ◽  
And Migration

scholarly journals The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity

2021 ◽  
Vol 33 (3) ◽  
pp. 565-580.e7
Author(s):  
Suzhen Chen ◽  
Xiaoxiao Liu ◽  
Chao Peng ◽  
Chang Tan ◽  
Honglin Sun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ampk Signaling ◽  
Signaling Axis

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

2016 ◽  
Vol 344 (2) ◽  
pp. 153-166 ◽  
Author(s):  
Yi-Chao Hsu ◽  
Chien-Yu Kao ◽  
Yu-Fen Chung ◽  
Don-Ching Lee ◽  
Jen-Wei Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Glioblastoma Cells ◽  
Fgfr Signaling ◽  
Signaling Axis

The sweet side of AMPK signaling: regulation of GFAT1

2017 ◽  
Vol 474 (7) ◽  
pp. 1289-1292 ◽  
Author(s):  
John W. Scott ◽  
Jonathan S. Oakhill
Keyword(s):  
Energy Demand ◽  
Dynamic Control ◽  
Cellular Protein ◽  
Post Translational Modification ◽  
Nutrient Metabolism ◽  
Ampk Signaling ◽  
Biochemical Journal ◽  
Signaling Axis ◽  
Hexosamine Biosynthesis ◽  
Living Organisms

Maintaining a steady balance between nutrient supply and energy demand is essential for all living organisms and is achieved through the dynamic control of metabolic processes that produce and consume adenosine-5′-triphosphate (ATP), the universal currency of energy in all cells. A key sensor of cellular energy is the adenosine-5′-monophosphate (AMP)-activated protein kinase (AMPK), which is the core component of a signaling network that regulates energy and nutrient metabolism. AMPK is activated by metabolic stresses that decrease cellular ATP, and functions to restore energy balance by orchestrating a switch in metabolism away from anabolic pathways toward energy-generating catabolic processes. A new study published in a recent issue of Biochemical Journal by Zibrova et al. shows that glutamine:fructose-6-phosphate amidotransferase-1 (GFAT1), the rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), is a physiological substrate of AMPK. The HBP is an offshoot of the glycolytic pathway that drives the synthesis of uridine-5′-diphospho-N-acetylglucosamine, the requisite donor metabolite needed for dynamic β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of cellular proteins. O-GlcNAcylation is a nutrient-sensitive post-translational modification that, like phosphorylation, regulates numerous intracellular processes. Zibrova et al. show that inhibitory phosphorylation of the GFAT1 residue Ser243 by AMPK in response to physiological or small-molecule activators leads to a reduction in cellular protein O-GlcNAcylation. Further work revealed that AMPK-dependent phosphorylation of GFAT1 promotes angiogenesis in endothelial cells. This elegant study demonstrates that the AMPK–GFAT1 signaling axis serves as an important communication point between two nutrient-sensitive signaling pathways and is likely to play a significant role in controlling physiological processes in many other tissues.

scholarly journals TMIC-51. GBP1 RECRUITS MACROPHAGES TO PROMOTE GLIOBLASTOMA GROWTH

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi259-vi259
Author(s):  
Lili Chen ◽  
Ming Li
Keyword(s):  
Macrophage Polarization ◽  
Tumor Development ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Orthotopic Mouse Model ◽  
Ccl2 Expression ◽  
Molecule Inhibitor ◽  
Signaling Axis ◽  
And Migration

Abstract Guanylate binding protein 1 (GBP1) is an interferon-inducible large GTPase which plays a key role in tumor development, but the molecular mechanism is poorly understood. Here we investigated whether GBP1 could influence the tumor microenvironment in glioblastoma, the most common and malignant brain tumor. We found that forced expression of GBP1 in glioblastoma cells induced macrophage polarization toward an M2 phenotype via upregulating Chemokine (C-C motif) ligand 2 (CCL2). CCL2 acted via its receptor C-C chemokine receptor 2 (CCR2) to enhance macrophage cell migration in vitro. The M2 macrophages in turn promoted glioblastoma cell proliferation and migration. The orthotopic mouse model showed that GBP1 recruited M2 macrophages into tumor to promote glioblastoma progression, and targeting CCL2/CCR2 signaling axis with a small molecule inhibitor RS504393 led to decreased macrophage attraction and M2 polarization and a significant tumor growth retardation and prolonged survival of tumor-bearing mice. Clinically, GBP1 expression positively correlated with M2 macrophage numbers and CCL2 expression in glioblastoma. Taken together, our results reveal that GBP1 modulates the tumor immune microenvironment through CCL2 induction to promote glioblastoma infiltrating growth, and targeting tumor-associated macrophages may represent a new therapeutic strategy against glioblastoma.

scholarly journals Prdx1 Promotes the Loss of Primary Cilia in Esophageal Squamous Cell Carcinoma

2019 ◽  
Author(s):  
Fanghua Gong ◽  
Qiongzhen Chen ◽  
Jinmeng Li ◽  
Xiaoning Yang ◽  
Junfeng Ma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Tumor Formation ◽  
Aurora A ◽  
Cilia Formation ◽  
Signaling Axis

Abstract Background: Loss of primary cilia is frequently observed in tumor cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction, the inability to exit the cell cycle, and promotion of tumor cell invasion. Primary cilia loss also occurs in esophageal squamous cell carcinoma (ESCC) cells, but the molecular mechanisms that explain how ESCC cells lose primary cilia remain poorly understood. Methods: Inhibiting the expression of Prdx1 in the ESCC cells to detect the up-regulated genes related to cilium regeneration and down-regulated genes related to cilium disassembly by Gene chip. And, mice and cell experiments were carried to confirm the role of the HEF1-Aurora A-HDAC6 signaling axis in ESCC. Results: In this study, we found that silencing Peroxiredoxin 1 (Prdx1) restores primary cilia formation, and over-expressing Prdx1 induces primary cilia loss in ESCC cells. We also showed that the expression of Prdx1 regulates the action of the HEF1-Aurora A-HDAC6 signaling axis to promote the disassembly of primary cilia, and suppression of Prdx1 results in decreased tumor formation and tumor mass volume in vivo. Conclusions: These results suggest that Prdx1 is a novel regulator of primary cilia formation in ESCC cells.

scholarly journals Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells

Theranostics ◽  
2020 ◽  
Vol 10 (15) ◽  
pp. 6928-6945
Author(s):  
Huizhen Sun ◽  
Husheng Wang ◽  
Xue Wang ◽  
Yoichi Aoki ◽  
Xinjing Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Glucose Metabolism ◽  
Cell Senescence ◽  
Aurora A ◽  
Signaling Axis
Sign in / Sign up

Export Citation Format

Share Document