Identification of two enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes.

Murakami, Takashi; Nishiyama, Takeshi; Shirotani, T.; Shinohara, Yasuo; Kan, Masaharu; Ishii, Kazuo; Kanai, Fumihiko; Nakazuru, S; Ebina, Yasuhiko

doi:10.1016/s0021-9258(19)50423-9

Cited by 118 publications

(13 citation statements)

References 45 publications

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“…Together, these data support the notion that mTOR promotes glycolysis to generate the necessary glycine to support enhanced collagen production. The observation that ATF4 mediates the stimulatory effects of TGF- 1 on SLC2A1 expression is further potentially in agreement with a previous study that identified two enhancer binding elements in the regulatory elements of the SLC2A1 gene that contain the same cyclic adenosine monophosphate response element consensus binding site shared by ATF4 (51).…”

Section: Discussionsupporting

confidence: 92%

mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β ₁ –induced collagen biosynthesis

et al. 2019

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The differentiation of fibroblasts into a transient population of highly activated, extracellular matrix (ECM)–producing myofibroblasts at sites of tissue injury is critical for normal tissue repair. Excessive myofibroblast accumulation and persistence, often as a result of a failure to undergo apoptosis when tissue repair is complete, lead to pathological fibrosis and are also features of the stromal response in cancer. Myofibroblast differentiation is accompanied by changes in cellular metabolism, including increased glycolysis, to meet the biosynthetic demands of enhanced ECM production. Here, we showed that transforming growth factor–β1 (TGF-β1), the key pro-fibrotic cytokine implicated in multiple fibrotic conditions, increased the production of activating transcription factor 4 (ATF4), the transcriptional master regulator of amino acid metabolism, to supply glucose-derived glycine to meet the amino acid requirements associated with enhanced collagen production in response to myofibroblast differentiation. We further delineated the signaling pathways involved and showed that TGF-β1–induced ATF4 production depended on cooperation between canonical TGF-β1 signaling through Smad3 and activation of mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). ATF4, in turn, promoted the transcription of genes encoding enzymes of the de novo serine-glycine biosynthetic pathway and glucose transporter 1 (GLUT1). Our findings suggest that targeting the TGF-β1–mTORC1–ATF4 axis may represent a novel therapeutic strategy for interfering with myofibroblast function in fibrosis and potentially in other conditions, including cancer.

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Section: Discussionsupporting

confidence: 92%

mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β ₁ –induced collagen biosynthesis

et al. 2019

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“…A major caveat for the interpretation of GLUT1 expression in cultured cells is the observation that GLUT1 expression is turned on or enhanced in most, if not all, cells in culture. This may be explained, at least partially, by the stress-response characteristics of GLUT1, including enhanced expression by serum factors and oncogenic transformation (Massa et al, 1996;Murakami et al, 1992). However, we have not detected GLUTs 2, 3, 4, or 5 in primary cortical astrocytes (Maher, 1995), thus supporting the contention that GLUT1 is the predominant glucose transporter isoform in cortical astrocytes.…”

Section: Glial Glucose Transporterssupporting

confidence: 58%

“…GLUT1 is the primary transporter of embryonic tissues (Bondy et al, 1992;Hogan et al, 1991), consistent with its function of supporting the basal metabolic needs of proliferating cells (Merrall et al, 1993). GLUT1 is uniformly detected in cells in culture and levels of GLUT1 mRNA and protein expression are affected by oncogenic transformation, as well as growth factors and activators of protein kinase C (Massa et al, 1996;Merrall et al, 1993;Murakami et al, 1992;Werner et al, 1981). In addition, GLUT1 mRNA and protein levels in vitro respond to ambient glucose concentrations by down-regulation in response to hexose concentrations above the normal range, and are enhanced in response to glucose deprivation (reviewed by Klip et al, 1994).…”

Section: Glut1mentioning

confidence: 95%

Glucose transporter proteins in brain: Delivery of glucose to neurons and glia

Vannucci¹,

Maher²,

Simpson³

1997

Glia

580

364

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Glucose is the principle energy source for the mammalian brain. Delivery of glucose from the blood to the brain requires transport across the endothelial cells of the blood‐brain barrier and into the neurons and glia. The facilitative glucose transporter proteins mediate these processes. The primary isoforms in brain are GLUT1, detected at high concentrations as a highly glycosylated form, (55 kDa) in blood‐brain barrier, and also as a less glycosylated, 45 kDa form, present in parenchyma, predominantly glia; GLUT3 in neurons; and GLUT5 in microglia. The rest of the transporter family, GLUTs 2, 4, and 7, have also been detected in brain but at lower levels of expression and confined to more discrete regions. All of the transporters probably contribute to cerebral glucose utilization, as part of overall metabolism and metabolic interactions among cells. We discuss the properties, regulation, cell‐specific location, and kinetic characteristics of the isoforms, their potential contributions to cerebral metabolism, and several experimental paradigms in which alterations in energetic demand and/or substrate supply affect glucose transporter expression. GLIA 21:2–21, 1997. © 1997 Wiley‐Liss, Inc.

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“…Previous studies have shown that mammalian cell oncogenic transformation is associated with numerous metabolic changes, particularly an increased rate of glucose transport. The glucose transporter GLUT1 can be stimulated by HIF-1α under hypoxic conditions by binding to cis-acting sites in the GLUT1 gene 59 flanking region ( 55 , 56 ). Wang et al ( 57 ) revealed that HIF-1α was capable of suppressing transcription of GLUT1 under hypoxic conditions in human glioblastoma cells.…”

Section: Discussionmentioning

confidence: 99%

miR‑143‑5p suppresses breast cancer progression by targeting the HIF‑1α‑related GLUT1 pathway

Li²,

Zhang

et al. 2022

Oncol Lett

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Breast cancer (BC) is a commonly identified life-threatening type of cancer and a major cause of death among women worldwide. Several microRNAs (miRs), including miR-143-5p, have been reported to be vital for regulating hallmarks of cancer; however, the effect of miR-143-5p on BC requires further exploration. The present study performed bioinformatics analysis on GSE42072 and GSE41922 datasets from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database to identify miR-143-5p expression patterns. Furthermore, miR-143-5p expression was detected in BC cell lines and tissues via reverse transcription-quantitative PCR. Post-transfection with miR-143-5p mimics, Cell Counting Kit-8, colony formation and Transwell assays were performed to explore the effects of miR-143-5p on BC cell proliferation, colony formation, and migration. The association of miR-143-5p with the hypoxia-inducible factor-1α (HIF-1α)-associated glucose transporter 1 (GLUT1) pathway was explored via western blotting, immunofluorescence and dual-luciferase reporter assay. The present study detected high expression of miR-143-5p in BC tissue of the GSE42072 and serum of the GSE41922 datasets by GEO chip analysis. Additionally, the expression levels of miR-143-5p were decreased in BC tissues compared with those in adjacent healthy tissues, and low miR-143-5p expression was associated with a poorer prognosis and shorter survival time in patients with BC. In vitro, miR-143-5p expression levels were decreased in BC cells, and transfection with miR-143-5p mimics suppressed BC cell proliferation, colony formation, migration. Furthermore, miR-143-5p targeted the HIF-1α-related GLUT1 pathway, and inhibited HIF-1α and GLUT1 expression. Additionally, HIF-1α agonists reversed the miR-143-5p-induced inhibition during tumorigenesis. In conclusion, miR-143-5p exhibited low expression in BC tissues, and suppressed BC cell proliferation, colony formation, migration. Moreover, the antitumor effects of miR-143-5p targeted the HIF-1α-related GLUT1 pathway.

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Identification of two enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes.

Cited by 118 publications

References 45 publications

mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β ₁ –induced collagen biosynthesis

mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β ₁ –induced collagen biosynthesis

Glucose transporter proteins in brain: Delivery of glucose to neurons and glia

miR‑143‑5p suppresses breast cancer progression by targeting the HIF‑1α‑related GLUT1 pathway

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Identification of two enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes.

Cited by 118 publications

References 45 publications

mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β 1 –induced collagen biosynthesis

mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β 1 –induced collagen biosynthesis

Glucose transporter proteins in brain: Delivery of glucose to neurons and glia

miR‑143‑5p suppresses breast cancer progression by targeting the HIF‑1α‑related GLUT1 pathway

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Resources

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mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β ₁ –induced collagen biosynthesis

mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β ₁ –induced collagen biosynthesis