Tumor cell‐derived angiopoietin‐like protein 2 establishes a preference for glycolytic metabolism in lung cancer cells

Osumi, Hironobu; Horiguchi, Haruki; Kadomatsu, Tsuyoshi; Tashiro, Kyosei; Morinaga, Jun; Takahashi, Takashi; Ikeda, Koei; Ito, Takaaki; Suzuki, Makoto; Endo, Motoyoshi; Oike, Yuichi

doi:10.1111/cas.14337

“…Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor that can have both autocrine and paracrine effects and it is involved in cell motility and invasiveness. In different lung cancer (LC) cellular models (NCI-H460, NCI-H460-LNM35, NCI-H1975, and HCC15), ANGPTL2 is responsible for an increase in GLUT3 expression (and an increase in glycolytic flux) via an integrin α5β1/ERK-dependent pathway impinging on TGFβ and its downstream factor ZEB1, concurrently with the execution of the EMT ( Figure 3 ) [ 172 ]. ANGPTL2 → integrin α5β1→ERK ⇒ TGFβ ↑ ⇒ ZEB1 ↑ ⇒ (GLUT3 ↑ & EMT) …”

Section: Emt and Metabolism In Selected Cancersmentioning

confidence: 99%

The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression

Fedele

¹

,

Sgarra

²

,

Battista

³

et al. 2022

IJMS

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The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate into the bloodstream via transdifferentiation into mesenchymal cells, a phenomenon known as epithelial–mesenchymal transition (EMT), and then reacquire the epithelial phenotype, the reverse process called mesenchymal–epithelial transition (MET), to colonize a new organ. During all metastatic stages, metabolic changes, which give cancer cells the ability to adapt to increased energy demand and to withstand a hostile new environment, are also important determinants of successful cancer progression. In this review, we describe the complex interaction between EMT and metabolism during tumor progression. First, we outline the main connections between the two processes, with particular emphasis on the role of cancer stem cells and LncRNAs. Then, we focus on some specific cancers, such as breast, lung, and thyroid cancer.

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“…TGF-β signaling pathway plays a pivotal role in inducing EMT. In lung cancer cells TGF-β could upregulate SLC2A3 expression through the EMT gene ZEB1 [ 59 ]. However, the link between TGF-β signaling and SLC2A3 expression is much less addressed and needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma

Chai

¹

,

Zhang

²

,

Fu

³

et al. 2023

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SLC2A3 is an important member of the glucose transporter superfamily. It has been recently suggested that upregulation of SLC2A3 is associated with poor survival and acts as a prognostic marker in a variety of tumors. Unfortunately, the prognostic role of SLC2A3 in head and neck squamous cell carcinoma (HNSC) is less known. In the present study, we analyzed SLC2A3 expression in HNSC and its correlation with prognosis using TCGA and GEO databases. The results showed that SLC2A3 mRNA expression was higher in HNSC compared with adjacent normal tissues, which was validated with our 9 pairs of HNSC specimens. Moreover, high SLC2A3 expression predicted poor prognosis in HNSC patients. Mechanistically, GSEA revealed that high expression of SLC2A3 was enriched in epithelial-mesenchymal transition (EMT) and NF-κB signaling. In HNSC cell lines, SLC2A3 knockdown inhibited cell proliferation and migration. In addition, NF-κB P65 and EMT-related gene expression was suppressed upon SLC2A3 knockdown, indicating that SLC2A3 may play a preeminent role in the progression of HNSC through the NF-κB/EMT axis. Meanwhile, the expression of SLC2A3 was negatively correlated with immune cells, suggesting that SLC2A3 may be involved in the immune response in HNSC. The correlation between SLC2A3 expression and drug sensitivity was further assessed. In conclusion, our study demonstrated that SLC2A3 could predict the prognosis of HNSC patients and mediate the progression of HNSC via the NF-κB/EMT axis and immune responses.

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“…Tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) activates tumor cell motility, invasiveness, and epithelial-mesenchymal transition to accelerate tumor metastasis in an autocrine/paracrine manner [ 36 ]. Recently, novel research indicated that stroma-derived ANGPTL2 could drive the production of immune-stimulated macrophages through the NF- κ B pathway and accelerate the activation of CD4 T helper 1 (Th1) cells to play an antitumor role [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Robust Immune-Related Prognostic Signature for Gastric Cancer

Huo

¹

,

Wu

²

,

Zang

³

2021

Journal of Immunology Research

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Background. An increasing number of reports have found that immune-related genes (IRGs) have a significant impact on the prognosis of a variety of cancers, but the prognostic value of IRGs in gastric cancer (GC) has not been fully elucidated. Methods. Univariate Cox regression analysis was adopted for the identification of prognostic IRGs in three independent cohorts (GSE62254, n = 300 ; GSE15459, n = 191 ; and GSE26901, n = 109 ). After obtaining the intersecting prognostic genes, the three independent cohorts were merged into a training cohort ( n = 600 ) to establish a prognostic model. The risk score was determined using multivariate Cox and LASSO regression analyses. Patients were classified into low-risk and high-risk groups according to the median risk score. The risk score performance was validated externally in the three independent cohorts (GSE26253, n = 432 ; GSE84437, n = 431 ; and TCGA, n = 336 ). Immune cell infiltration (ICI) was quantified by the CIBERSORT method. Results. A risk score comprising nine genes showed high accuracy for the prediction of the overall survival (OS) of patients with GC in the training cohort ( AUC > 0.7 ). The risk of death was found to have a positive correlation with the risk score. The univariate and multivariate Cox regression analyses revealed that the risk score was an independent indicator of the prognosis of patients with GC ( p < 0.001 ). External validation confirmed the universal applicability of the risk score. The low-risk group presented a lower infiltration level of M2 macrophages than the high-risk group ( p < 0.001 ), and the prognosis of patients with GC with a higher infiltration level of M2 macrophages was poor ( p = 0.011 ). According to clinical correlation analysis, compared with patients with the diffuse and mixed type of GC, those with the Lauren classification intestinal GC type had a significantly lower risk score ( p = 0.00085 ). The patients’ risk score increased with the progression of the clinicopathological stage. Conclusion. In this study, we constructed and validated a robust prognostic signature for GC, which may help improve the prognostic assessment system and treatment strategy for GC.

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Tumor cell‐derived angiopoietin‐like protein 2 establishes a preference for glycolytic metabolism in lung cancer cells

Cited by 22 publications

References 41 publications

The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression

The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression

Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma

Development and Validation of a Robust Immune-Related Prognostic Signature for Gastric Cancer

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