Polymorphisms of monocarboxylate transporter genes are associated with clinical outcomes in patients with colorectal cancer

Fei, Fei; Guo, Xu; Chen, Yibing; Liu, Xiaonan; Tu, Jianfei; Xing, Jinliang; Chen, Zhinan; Ji, Jiansong; He, Xianli

doi:10.1007/s00432-014-1877-y

Cited by 19 publications

(11 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the recently recognized hallmarks of cancer is altered glucose metabolism with dependence on glycolysis for energy production [ 4 ]. Consequently, large amounts of lactate produced have to be exported to the extracellular milieu; thus, it is not surprising that cancer cells exhibit high levels of MCT expression to maintain this metabolic phenotype [ 9 , 10 ]. In this context, MCT1 and MCT4 on one hand play a dual role in the maintenance of high glycolytic rates by performing lactate efflux, and on the other hand contribute to the homeostasis of the intracellular pH through the cotransport of protons [ 81 ].…”

Section: Mcts In Tumorsmentioning

confidence: 99%

The altered glucose metabolism in tumor and a tumor acidic microenvironment associated with extracellular matrix metalloproteinase inducer and monocarboxylate transporters

Dong

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Extracellular matrix metalloproteinase inducer, also knowns as cluster of differentiation 147 (CD147) or basigin, is a widely distributed cell surface glycoprotein that is involved in numerous physiological and pathological functions, especially in tumor invasion and metastasis. Monocarboxylate transporters (MCTs) catalyze the proton-linked transport of monocarboxylates such as L-lactate across the plasma membrane to preserve the intracellular pH and maintain cell homeostasis. As a chaperone to some MCT isoforms, CD147 overexpression significantly contributes to the metabolic transformation of tumor. This overexpression is characterized by accelerated aerobic glycolysis and lactate efflux, and it eventually provides the tumor cells with a metabolic advantage and an invasive phenotype in the acidic tumor microenvironment. This review highlights the roles of CD147 and MCTs in tumor cell metabolism and the associated molecular mechanisms. The regulation of CD147 and MCTs may prove to be with a therapeutic potential for tumors through the metabolic modification of the tumor microenvironment.

show abstract

Section: Mcts In Tumorsmentioning

confidence: 99%

The altered glucose metabolism in tumor and a tumor acidic microenvironment associated with extracellular matrix metalloproteinase inducer and monocarboxylate transporters

Dong

et al. 2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…SLC16A1 rs1049434 (in near-perfect LD with rs7169 and rs7556664) was studied the most due to its exonic location, and the fact that it affects MCT1 protein structure [ 22 , 23 , 24 , 25 ]. It has been shown that the mutated variant (containing Glu in the protein sequence and T in the DNA sequence) exhibits increased lactate transport via SLA16A1, as compared to the wild type Asp/A [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

BSG and MCT1 Genetic Variants Influence Survival in Multiple Myeloma Patients

Łacina

Butrym

Mazur

et al. 2018

Genes

View full text Add to dashboard Cite

Multiple myeloma (MM) is a haematologic malignancy characterized by the presence of atypical plasma cells. Basigin (BSG, CD147) controls lactate export through the monocarboxylic acid transporter 1 (MCT1, SLC16A1) and supports MM survival and proliferation. Additionally, BSG is implicated in response to treatment with immunomodulatory drugs (thalidomide and its derivatives). We investigated the role of single nucleotide polymorphisms (SNPs) in the gene coding for BSG and SLC16A1 in MM. Following an in silico analysis, eight SNPs (four in BSG and four in SLC16A1) predicted to have a functional effect were selected and analyzed in 135 MM patients and 135 healthy individuals. Alleles rs4919859 C, rs8637 G, and haplotype CG were associated with worse progression-free survival (p = 0.006, p = 0.017, p = 0.002, respectively), while rs7556664 A, rs7169 T and rs1049434 A (all in linkage disequilibrium (LD), r2 > 0.98) were associated with better overall survival (p = 0.021). Similar relationships were observed in thalidomide-treated patients. Moreover, rs4919859 C, rs8637 G, rs8259 A and the CG haplotype were more common in patients in stages II–III of the International Staging System (p < 0.05), while rs8259 A correlated with higher levels of β-2-microglobulin and creatinine (p < 0.05). Taken together, our results show that BSG and SLC16A1 variants affect survival, and may play an important role in MM.

show abstract

“…In addition, induction of MCT1 expression has been observed with GHB and butyrate exposure (46,47) indicating that chronic exposure to MCT substrates may lead to increased expression levels. Few studies are available assessing the impact of polymorphic variants of MCTs/SMCTs on transporter function; recent studies have identified potential functional MCT polymorphisms that influence plasma lactate accumulation (48) and prognosis in colorectal cancer (49). Future studies should assess the impact of altered MCT expression on the distribution and toxicokinetics of GHB.…”

Section: Discussionmentioning

confidence: 99%

The Drug of Abuse Gamma-Hydroxybutyric Acid Exhibits Tissue-Specific Nonlinear Distribution

Felmlee

Morse

Follman

et al. 2017

AAPS J

View full text Add to dashboard Cite

The drug of abuse γ-hydroxybutyric acid (GHB) demonstrates complex toxicokinetics with dose-dependent metabolic and renal clearance. GHB is a substrate of monocarboxylate transporters (MCTs) which are responsible for the saturable renal reabsorption of GHB. MCT expression is observed in many tissues and therefore may impact the tissue distribution of GHB. The objective of the present study was to evaluate the tissue distribution kinetics of GHB at supratherapeutic doses. GHB (400, 600, and 800 mg/kg iv) or GHB 600 mg/kg plus L-lactate (330 mg/kg iv bolus followed by 121 mg/kg/h infusion) was administered to rats and blood and tissues were collected for up to 330 min post-dose. K values for GHB varied in both a tissue- and dose-dependent manner and were less than 0.5 (except in the kidney). Nonlinear partitioning was observed in the liver (0.06 at 400 mg/kg to 0.30 at 800 mg/kg), kidney (0.62 at 400 mg/kg to 0.98 at 800 mg/kg), and heart (0.15 at 400 mg/kg to 0.29 at 800 mg/kg), with K values increasing with dose consistent with saturation of transporter-mediated efflux. In contrast, lung partitioning decreased in a dose-dependent manner (0.43 at 400 mg/kg to 0.25 at 800 mg/kg) suggesting saturation of active uptake. L-lactate administration decreased K values in liver, striatum, and hippocampus and increased K values in lung and spleen. GHB demonstrates tissue-specific nonlinear distribution consistent with the involvement of monocarboxylate transporters. These observed complexities are likely due to the involvement of MCT1 and 4 with different affinities and directionality for GHB transport.

show abstract

Polymorphisms of monocarboxylate transporter genes are associated with clinical outcomes in patients with colorectal cancer

Abstract: Our findings suggest that SNPs in MCT1 and MCT2 genes may affect clinical outcomes and can be used to predict the response to adjuvant chemotherapy in CRC patients who received surgical treatment once validated in future study.

Cited by 19 publications

References 37 publications

The altered glucose metabolism in tumor and a tumor acidic microenvironment associated with extracellular matrix metalloproteinase inducer and monocarboxylate transporters

The altered glucose metabolism in tumor and a tumor acidic microenvironment associated with extracellular matrix metalloproteinase inducer and monocarboxylate transporters

BSG and MCT1 Genetic Variants Influence Survival in Multiple Myeloma Patients

The Drug of Abuse Gamma-Hydroxybutyric Acid Exhibits Tissue-Specific Nonlinear Distribution

Contact Info

Product

Resources

About