Elevation of adenylate energy charge by angiopoietin-like 4 enhances epithelial–mesenchymal transition by inducing 14-3-3γ expression

Teo, Ziqiang; Sng, Ming Keat; Chan, Jeremy Soon Kiat; Lim, Maegan Miang Kee; Li, Yinliang; Li, Luchun; Phua, Terri; Lee, J. Y. H.; Tan, Zhen; Zhu, Pengcheng; Tan, Nguan Soon

doi:10.1038/onc.2017.244

Cited by 45 publications

(51 citation statements)

References 50 publications

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“…In this study, it is worth noting that PGE 2 ‐induced EMT markers, including Snail, Slug, Twist, and fibronectin, and MMPs were reduced with the depletion of ANGPTL4 in HNSCC. These results were consistent with the finding that ANGPTL4‐regulated EMT participated in various tumor metastases 5,47 . In addition to the regulation of EMT, ANGPTL4 enhances vascular permeability through the integrin pathway to promote tumor metastasis 7 .…”

Section: Discussionsupporting

confidence: 90%

Epidermal growth factor‐induced COX‐2 regulates metastasis of head and neck squamous cell carcinoma through upregulation of angiopoietin‐like 4

et al. 2020

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Epidermal growth factor receptor (EGFR) expression and activation are the major causes of metastasis in cancers such as head and neck squamous cell carcinoma (HNSCC). However, the reciprocal effect of EGF‐induced COX‐2 and angiopoietin‐like 4 (ANGPTL4) on HNSCC metastasis remains unclear. In this study, we revealed that the expression of ANGPTL4 is essential for COX‐2‐derived prostaglandin E2 (PGE2)‐induced tumor cell metastasis. We showed that EGF‐induced ANGPTL4 expression was dramatically inhibited with the depletion and inactivation of COX‐2 by knockdown of COX‐2 and celecoxib treatment, respectively. Prostaglandin E2 induced ANGPTL4 expression in a time‐ and dose‐dependent manners in various HNSCC cell lines through the ERK pathway. In addition, the depletion of ANGPTL4 and MMP1 significantly impeded the PGE2‐induced transendothelial invasion ability of HNSCC cells and the binding of tumor cells to endothelial cells. The induction of molecules involved in the regulation of epithelial‐mesenchymal transition was also dependent on ANGPTL4 expression in PGE2‐treated cells. The depletion of ANGPTL4 further blocked PGE2‐primed tumor cell metastatic seeding of lungs. These results indicate that the EGF‐activated PGE2/ANGPTL4 axis enhanced HNSCC metastasis. The concurrent expression of COX‐2 and ANGPTL4 in HNSCC tumor specimens provides insight into potential therapeutic targets for the treatment of EGFR‐associated HNSCC metastasis.

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Section: Discussionsupporting

confidence: 90%

Epidermal growth factor‐induced COX‐2 regulates metastasis of head and neck squamous cell carcinoma through upregulation of angiopoietin‐like 4

et al. 2020

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“…From this, a prognostic prediction model was constructed, the RiskScore of patients was calculated, and prediction and verification were also carried out. Among all 14 prognosis-specific immunerelated genes, 9 (e.g., PSMD11, PPIA, MIF, BMP5, DKK1, PDGFB, ANGPTL4, IL1R2, and THRB) (26)(27)(28)(29)(30)(31)(32)(33)(34) have been reported to be involved in the immune microenvironmentassociated pathogenesis of lung adenocarcinoma or suggested to be significant predictors of recurrence-free or overall survival. This implies that our bioinformatics analysis using TCGA and ImmPort cohorts has prognostic value.…”

Section: Discussionmentioning

confidence: 99%

An Immune-Related Signature Predicts Survival in Patients With Lung Adenocarcinoma

et al. 2019

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We investigated the local immune status and its prognostic value in lung adenocarcinoma. In total, 513 lung adenocarcinoma samples from TCGA and ImmPort databases were collected and analyzed. The R package coxph was employed to mine immune-related genes that were significant prognostic indicators using both univariate and multivariate analyses. The R software package glmnet was then used for Lasso Cox regression analysis, and a prognosis prediction model was constructed for lung adenocarcinoma; clusterProfiler was selected for functional gene annotations and KEGG enrichment analysis. Finally, correlations between the RiskScore and clinical features or signaling pathways were established. Sixty-four immune-related genes remarkably correlated with patient prognosis and were further applied. Samples were hierarchically clustered into two subgroups. Accordingly, the LASSO regression algorithm was employed to screen the 14 most representative immune-related genes (PSMD11,

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“…The real-time qPCR and immunoblot analyses were performed as previously described [50,51]. The sequences of primers for qPCR are in Table S2.…”

Section: Real-time Pcr (Qpcr) and Immunoblot Analysesmentioning

confidence: 99%

PPARβ/δ Agonism Upregulates Forkhead Box A2 to Reduce Inflammation in C2C12 Myoblasts and in Skeletal Muscle

Phua

Tan

Yip

et al. 2020

IJMS

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Daily activities expose muscles to innumerable impacts, causing accumulated tissue damage and inflammation that impairs muscle recovery and function, yet the mechanism modulating the inflammatory response in muscles remains unclear. Our study suggests that Forkhead box A2 (FoxA2), a pioneer transcription factor, has a predominant role in the inflammatory response during skeletal muscle injury. FoxA2 expression in skeletal muscle is upregulated by fatty acids and peroxisome proliferator-activated receptors (PPARs) but is refractory to insulin and glucocorticoids. Using PPARβ/δ agonist GW501516 upregulates FoxA2, which in turn, attenuates the production of proinflammatory cytokines and reduces the infiltration of CD45+ immune cells in two mouse models of muscle inflammation, systemic LPS and intramuscular injection of carrageenan, which mimic localized exercise-induced inflammation. This reduced local inflammatory response limits tissue damage and restores muscle tetanic contraction. In line with these results, a deficiency in either PPARβ/δ or FoxA2 diminishes the action of the PPARβ/δ agonist GW501516 to suppress an aggravated inflammatory response. Our study suggests that FoxA2 in skeletal muscle helps maintain homeostasis, acting as a gatekeeper to maintain key inflammation parameters at the desired level upon injury. Therefore, it is conceivable that certain myositis disorders or other forms of painful musculoskeletal diseases may benefit from approaches that increase FoxA2 activity in skeletal muscle.

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Elevation of adenylate energy charge by angiopoietin-like 4 enhances epithelial–mesenchymal transition by inducing 14-3-3γ expression

Cited by 45 publications

References 50 publications

Epidermal growth factor‐induced COX‐2 regulates metastasis of head and neck squamous cell carcinoma through upregulation of angiopoietin‐like 4

Epidermal growth factor‐induced COX‐2 regulates metastasis of head and neck squamous cell carcinoma through upregulation of angiopoietin‐like 4

An Immune-Related Signature Predicts Survival in Patients With Lung Adenocarcinoma

PPARβ/δ Agonism Upregulates Forkhead Box A2 to Reduce Inflammation in C2C12 Myoblasts and in Skeletal Muscle

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