GLUT1 regulates cell glycolysis and proliferation in prostate cancer

Xiao, Hengjun; Wang, Jun; Yan, Weixin; Cui, Yubin; Chen, Zheng; Gao, Xin; Wen, Xin; Chen, Jun

doi:10.1002/pros.23448

Cited by 131 publications

(99 citation statements)

References 29 publications

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“…Glut1 is a well-known glycolysis-related element that can metabolize glucose to produce ATP. A recent study corroborates that Glut1 often acts as a glucose transporter to regulate cancer cell proliferation and invasion-metastasis potential by mediating glycolysis in various carcinomas [8,21,25]. Intriguingly, the current data substantiated that KLK10 depression decreased the expression of Glut1.…”

Section: Discussionsupporting

confidence: 84%

Kallikrein-related peptidase (KLK10) cessation blunts colorectal cancer cell growth and glucose metabolism by regulating the PI3K/Akt/mTOR pathway

Wei

Dong

Shen

2020

neo

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Colorectal cancer (CRC) is a common aggressive carcinoma with a proverbial feature of metabolic reprogramming that is essential for cancer cell growth. Recent research corroborates the controversial function of kallikrein-related peptidase 10 (KLK10) in cancer. However, its role and underlying mechanism in CRC remains elusive. In the present study, high expression of KLK10 was detected in CRC cell lines. Knockdown of KLK10 expression by a specific siRNA inhibited cell proliferation, evoked cell apoptosis, and increased caspase-3 activity in HT29 CRC cells. Furthermore, KLK10 suppression also afforded the suppressive effects on glycolysis in CRC cells as the data showed that targeting KLK10 restrained glucose uptake, lactate production, and glycolysis-related glucose transporter 1 (Glut1) expression. Mechanism analysis corroborated that cessation of KLK10 muted the PI3K/AKT-mTOR signaling. Intriguingly, reactivating the PI3K/AKT-mTOR pathway by its agonist IGF-1 notably reversed the inhibitory effects of KLK10 cessation on CRC cell growth and glucose metabolism. More important, preconditioning with PI3K/AKT inhibitor LY294002 or mTOR inhibitor rapamycin both aggravated KLK10 knockdown-suppressed cancer cell growth and glucose metabolism. These findings suggest that KLK10 silencing may attenuate the progression of CRC by inhibiting cell growth and glycolysis via the PI3K/AKT/mTOR signaling, supporting a potential and promising target for CRC therapy.

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Section: Discussionsupporting

confidence: 84%

Kallikrein-related peptidase (KLK10) cessation blunts colorectal cancer cell growth and glucose metabolism by regulating the PI3K/Akt/mTOR pathway

Wei

Dong

Shen

2020

neo

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“…Our analysis shows that cell proliferation gene set is higher in glycolysis-high tumors relative to glycolysis-low tumors which is also mentioned by other studies [33] . As we know production of proteins, lipids and nucleic acids is essential for a successful replicative cell division thus promote cell proliferation [34] .…”

Section: Discussionsupporting

confidence: 89%

Persistent cell proliferation signals correlates with increased glycolysis in tumor hypoxia microenvironment across cancer types

Wei

Huang

et al. 2020

Preprint

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Background：Altered metabolism is a hallmark of cancer and glycolysis is one of the important factors promoting tumor development. Given that the absence of multi-sample big data research about glycolysis, the molecular mechanisms involved in glycolysis or the relationships between glycolysis and tumor microenvironment are not fully studied. Thus, a more comprehensive approach in a pan-cancer landscape may be needed.Methods: Here, we develop a computational pipeline to study multi-omics molecular features defining glycolysis activity and identify molecular alterations that correlate with glycolysis.We apply a 22-gene expression signature to define the glycolysis activity landscape and verify the robustness using clinically defined glycolysis samples from several previous studies. Based on gene expression signature, we classify about 5552 of 9229 tumor samples into glycolysis score-high and score-low groups across 25 cancer types from The Cancer Genome Atlas (TCGA) and demonstrate their prognostic associations. Moreover, using genomes and transcriptome data, we characterize the association of copy-number aberrations (CNAs), somatic single-nucleotide variants (SNVs) and hypoxia signature with glycolysis activity.Findings: Gene set variation analysis (GSVA) score by gene set expression was verified robustly to represent glycolytic activity and highly glycolytic tumors presented a poor overall survival in some cancer types. Then, we identified various types of molecular features promoting tumor cell proliferation were associated with glycolysis activity. Our study showed that TCA cycle and respiration electron transport were active in glycolysis-high tumors, indicating glycolysis was not a symptom of impaired oxidative metabolism. The glycolytic score significantly correlated with hypoxia score across all 3 cancer types. Glycolysis score was also associated with elevated genomic instability. In all tumor types, high glycolysis tumors exhibited characteristic driver genes altered by CNAs identified multiple oncogenes and tumor suppressors. We observed widespread glycolysis-associated dysregulation of mRNA across cancers and screened out HSPA8 and P4HA1 as the potential modulating factor to glycolysis. Besides, the expression of genes encoding glycolytic enzymes positively correlated with genes in cell cycle.Interpretation: This is the first study to identify gene expression signatures that reflect glycolysis activity, which can be easily applied to large numbers of patient samples. Our analysis establishes a computational framework for characterizing glycolysis activity using gene expression data and defines correlation of glycolysis with the hypoxia microenvironment, tumor cell cycle and proliferation at a pan-cancer landscape. The findings suggest that the mechanisms whereby hypoxia influence glycolysis are likely multifactorial.Our finding is significant not just in demonstrating definition value for glycolysis but also in providing a comprehensive molecular-level understanding of glycolysis and suggesting a framewo...

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“…The expression of ubiquitous glucose transporter, GLUT1, was elevated by androgen treatment in these cells. A recent study has further validated the critical role played by GLUT1 in PCa, the knockdown of which inhibited glycolysis, cell proliferation and induced cycle arrest at G2/M phase (Xiao et al 2018). Other GLUT isoforms like GLUT3 (Vaz et al 2012), insulin-sensitive isoforms GLUT4, GLUT12 (Chandler et al 2003) and fructose transporter GLUT5 (Reinicke et al 2012) are also reported in PCa cells.…”

Section: Metabolite Transportersmentioning

confidence: 82%

The impact of transcription on metabolism in prostate and breast cancers

Poulose¹,

Mills²,

Steele³

2018

Endocrine-Related Cancer

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Metabolic dysregulation is regarded as an important driver in cancer development and progression. The impact of transcriptional changes on metabolism has been intensively studied in hormone-dependent cancers, and in particular, in prostate and breast cancer. These cancers have strong similarities in the function of important transcriptional drivers, such as the oestrogen and androgen receptors, at the level of dietary risk and epidemiology, genetics and therapeutically. In this review, we will focus on the function of these nuclear hormone receptors and their downstream impact on metabolism, with a particular focus on lipid metabolism. We go on to discuss how lipid metabolism remains dysregulated as the cancers progress. We conclude by discussing the opportunities that this presents for drug repurposing, imaging and the development and testing of new therapeutics and treatment combinations.

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GLUT1 regulates cell glycolysis and proliferation in prostate cancer

Abstract: GLUT1 may play an important role in PCa progression via mediating glycolysis and proliferation. Our study also indicated a potential crosstalk between GLUT1-mediated glycolysis and androgen sensitivity in PCa.

Cited by 131 publications

References 29 publications

Kallikrein-related peptidase (KLK10) cessation blunts colorectal cancer cell growth and glucose metabolism by regulating the PI3K/Akt/mTOR pathway

Kallikrein-related peptidase (KLK10) cessation blunts colorectal cancer cell growth and glucose metabolism by regulating the PI3K/Akt/mTOR pathway

Persistent cell proliferation signals correlates with increased glycolysis in tumor hypoxia microenvironment across cancer types

The impact of transcription on metabolism in prostate and breast cancers

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