Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma: analysis of TCGA data

Kim, Eun Young; Jung, Sua; Park, Won Seo; Lee, Joon Hyop; Shin, Rumi; Heo, Seung Chul; Choe, Eun Kyung; Lee, Jae Hyun; Kim, Kwangsoo; Chai, Young Jun

doi:10.1186/s12885-019-5475-x

Cited by 45 publications

(37 citation statements)

References 26 publications

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Section: Discussioncontrasting

confidence: 92%

“…and GLUT2 overexpression has been linked to poor patient outcome [44,96,97]. Interestingly, we found a reduction in GLUT3, as opposed to the ndings in other studies where they have shown upregulation of GLUT3 and its link to poor overall survival [44,96]. Still, research by Younes in 1997 on 289 lung adenocarcinoma samples suggested that GLUT3 overexpression is reported to be mostly found in combination with GLUT1 overexpression as only 21% were positive for both GLUT1 and GLUT3 [98].…”

Section: Discussioncontrasting

confidence: 82%

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Inhibition of pyruvate dehydrogenase kinase redirects NSCLC cell metabolism and counteracts development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors

Dyrstad¹,

Lotsberg²,

Tan³

et al. 2020

Preprint

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Background Non-small cell lung cancer (NSCLC) patients harboring oncogenic mutations in the epidermal growth factor receptor (EGFR) inevitably develop resistance to targeted therapy. Drug resistance is an example of cancer cell plasticity where cells change according to diverse microenvironmental pressure, which can be described as a way of evolution by natural selection. Metabolic rewiring during cancer development may support several malignant features and facilitate emergence of therapy resistant clones. Results Analysis of transcriptome data from two independent NSLSC patient cohorts identified upregulated markers of glucose metabolism and ROS defense in tumors compared to normal tissue. We show that these alterations were associated with increased expression of pyruvate dehydrogenase kinase 1 (PDK1). We established relevant in vitro models to study metabolic alterations in the context of resistance to EGFR TKIs to determine if targeted metabolic intervention would prevent development of resistance to EGFR tyrosine kinase inhibitors (EGFR TKIs) in NSCLC cells. The PDK inhibitor dichloroacetate (DCA) was shown to reduce cell growth. This mechanism was associated with redirected metabolism towards pyruvate and lactate oxidation, and reduced lactate production, both in EGFR TKI sensitive and resistant NSCLC cells. Conclusion We propose that the intracellular stress created by redirecting pyruvate metabolism can prevent EGFR TKI resistance in NSCLC.

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Section: Discussioncontrasting

confidence: 92%

Section: Discussioncontrasting

confidence: 82%

Inhibition of pyruvate dehydrogenase kinase redirects NSCLC cell metabolism and counteracts development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors

Dyrstad¹,

Lotsberg²,

Tan³

et al. 2020

Preprint

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show abstract

“…GLUT3 expression is found to be high in non-small cell lung cancer and that correlates to poor prognosis compared to other lung cancer types [31]. In addition, SLC2A3, the gene of GLUT3, is upregulated in high mortality colorectal carcinoma patients based on the TCGA dataset [32]. Additionally, in the brain, GLUT3 is also overexpressed in aggressive brain cancer cells and could impact the drug resistant ability [14,15].…”

Section: Discussionmentioning

confidence: 99%

Glucose Transporter 3 Is Essential for the Survival of Breast Cancer Cells in the Brain

Kuo

Chang

Yeh

et al. 2019

Cells

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Breast cancer brain metastasis commonly occurs in one-fourth of breast cancer patients and is associated with poor prognosis. Abnormal glucose metabolism is found to promote cancer metastasis. Moreover, the tumor microenvironment is crucial and plays an active role in the metabolic adaptations and survival of cancer cells. Glucose transporters are overexpressed in cancer cells to increase glucose uptake. The glucose transporter 3 (GLUT3) is a high-affinity glucose transporter that is highly expressed in mammalian neurons. GLUT3 is also overexpressed in several malignant brain tumors. However, the role of GLUT3 in breast cancer brain metastasis remains unknown. The results of the present study demonstrated that GLUT3 is highly overexpressed in brain metastatic breast cancers and mediates glucose metabolic reprogramming. Furthermore, knockdown of cAMP-response element binding protein (CREB) could directly regulate GLUT3 expression in brain metastatic breast cancer cells. Notably, we verified and provided a novel role of GLUT3 in mediating glucose metabolism and assisting breast cancer cells to survive in the brain to promote brain metastasis.

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“…Among its 14 members, GLUT1 is broadly expressed in various cancer cells and plays a pivotal role in glycolytic metabolism . Interestingly, a recent report indicates that GLUT3 is also expressed in glioblastoma, colon cancer, and lung cancer, suggesting that GLUT3 also functions in metabolic activity in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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We previously revealed that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates the metastatic capacity of tumors in an autocrine/paracrine manner by activating tumor cell motility and invasiveness and the epithelial-mesenchymal transition. However, the effects of ANGPTL2 on cancer cell glycolytic metabolism, which is a hallmark of tumor cells, are unknown. Here we report evidence supporting a role for tumor cell-derived ANGPTL2 in establishing a preference for glycolytic metabolism. We report that a highly metastatic lung cancer cell subline expressing abundant ANGPTL2 showed upregulated expression of the glucose transporter GLUT3 as well as enhanced glycolytic metabolism relative to a less metastatic parental line. Most notably, ANGPTL2 overexpression in the less metastatic line activated glycolytic metabolism by increasing GLUT3 expression. Moreover, ANGPTL2 signaling through integrin α5β1 increased GLUT3 expression by increasing transforming growth factor-β (TGF-β) signaling and expression of the downstream transcription factor zinc finger E-box binding homeobox 1 (ZEB1). Conversely, ANGPTL2 knockdown in the highly metastatic subline decreased TGF-β1, ZEB1, and GLUT3 expression and antagonized glycolytic metabolism. In primary tumor cells from patients with lung cancer, ANGPTL2 expression levels correlated with GLUT3 expression. Overall, this work suggests that tumor cell-derived ANGPTL2 accelerates activities associated with glycolytic metabolism in lung cancer cells by activating TGF-β-ZEB1-GLUT3 signaling. K E Y W O R D SANGPTL2, cancer metabolism, GLUT3, lung cancer, ZEB1

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Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma: analysis of TCGA data

Cited by 45 publications

References 26 publications

Inhibition of pyruvate dehydrogenase kinase redirects NSCLC cell metabolism and counteracts development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors

Inhibition of pyruvate dehydrogenase kinase redirects NSCLC cell metabolism and counteracts development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors

Glucose Transporter 3 Is Essential for the Survival of Breast Cancer Cells in the Brain

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

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