Evaluation of MCT1, MCT4 and CD147 Genes in Peripheral Blood Cells of Breast Cancer Patients and Their Potential Use as Diagnostic and Prognostic Markers

Luz, Maria Cláudia de Brito; Perez, Matheus Moreira; Azzalis, Ligia Ajaime; Sousa, Luiz Vinícius de Alcântara; Adami, Fernando; Fonseca, Fernando L. A.; Alves, Beatriz da Costa Aguiar

doi:10.3390/ijms18040170

Cited by 17 publications

(16 citation statements)

References 37 publications

(49 reference statements)

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“…Although extensive studies can be readily available regarding the MCT1 in cancers of different types; it has been little described in esophageal cancer with the exception of two recent related reports [17,18]: one about MCT1 expression in Barrett's esophagus and adenocarcinoma, the other ESCC. Analysis from previous investigations concerning MCT1 in cancers, regardless of different types [19][20][21][22], revealed that MCT1 prevailed or predominantly over-expressed in cancerous tissues as compared with normal controls and up-regulated MCT1 was found to be linked with poor outcome as well as tumor metastases, which was fully in agreement with our observations in ESCC of our own case. What's congruent with our description with regard to MCT1 is that, in a recent study [18] by Chen X and colleagues, MCT1 was exhibited to be an independent prognostic factor in ESCC.…”

Section: Discussionsupporting

confidence: 92%

Clinicopathological and prognostic involvements of MCT1, MCT4 and IL7R in esophageal squamous cell carcinoma

Liu

Tan

Shen

et al. 2019

Preprint

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BackgroundMCTs, short for monocarboxylate transporters, especially MCT1 and MCT4, have been widely touched upon in a variety of immune and cancer cells; however, they have been rarely described in esophageal squamous cell carcinoma (ESCC). IL7R, receptor of interleukin 7, has been shown to operate in several cancers; though, the clinicopathological implication of IL7R expression in ESCC remains less known. MethodsHerein, to understand the clinicopathological involvements of MCT1, MCT4 and IL7R expression in ESCC, immunohistochemistry was performed with ESCC tissue microarray comprising 86 paired ESCC and its matched normal control dots. Subsequently, statistical analyses ensued. ResultsIt was shown that concomitant expression of MCT1, MCT4 and IL7R prevailed in the stromal compartment of ESCC tissues relative to the epithelial. Moreover, up-regulated MCT1 and MCT4 were markedly associated with tumor size; while IL7R was displayed to closely correlate with lymph node metastases and clinical stage. Elevated MCT1, MCT4 and IL7R were strikingly associated with adverse outcome of ESCC. ConclusionsTogether, the data we presented here indicate that MCT1/4 and IL7R were heavily involved in the oncogenesis of ESCC.

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Section: Discussionsupporting

confidence: 92%

Clinicopathological and prognostic involvements of MCT1, MCT4 and IL7R in esophageal squamous cell carcinoma

Liu

Tan

Shen

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 92%

Clinicopathological and prognostic involvements of MCT1, MCT4 and IL-7R in esophageal squamous cell carcinoma

Liu

Tan

et al. 2020

Preprint

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Background: MCTs, short for monocarboxylate transporters, especially MCT1 and MCT4, have been widely touched upon in a variety of immune and cancer cells; however, they have been rarely described in esophageal squamous cell carcinoma (ESCC). IL7R, receptor of interleukin 7, has been shown to operate in several cancers; though, the clinicopathological implication of IL7R expression in ESCC remains less known.Methods: Herein, to understand the clinicopathological involvements of MCT1, MCT4 and IL7R in ESCC, immunohistochemistry was performed with ESCC tissue microarray comprising 86 paired ESCC and its matched normal control dots. Post-hoc statistical analyses were undertaken with Cross-table and survival analyses. Results: It was shown that concomitant expression of MCT1, MCT4 and IL7R prevailed in the stromal compartment of ESCC tissues relative to the epithelial. Moreover, upregulated MCT1 and MCT4 were markedly associated with tumor size; while IL7R was displayed to closely correlate with lymph node metastases and clinical stage. Elevated MCT1, MCT4 and IL7R were strikingly associated with adverse outcome of ESCC.Conclusions: Together, the data we presented here indicate that MCT1/4 and IL7R were heavily involved in the oncogenesis of ESCC. BackgroundMonocarboxylic acid, including lactate, pyruvate and ketone bodies, have been found to play major roles in cancer metabolism and must be transported across both the plasma and mitochondrial membranes [1], where monocarboxylate transporter (abbreviated as MCT) family actually take charge of the process. MCT family now comprises as many as 14 members, of which only the first four, that is, from MCT1 to MCT4, have been experimentally borne out to catalyze the transport of monocarboxylates, such as lactate, pyruvate and ketone bodies [1,2], which come to be recognized as important metabolic fuel for cancer cells. Given this, there is a need to understand the clinicopathological as well as prognostic implication of MCT1 and MCT4 expression in ESCC, where it has been little described surrounding MCT1 and MCT4 expression and its significance.Lactate, as mentioned above, has been shown to be as an important metabolic fuel for normal cells in

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“…Monocarboxylic acid transporter 4 (SLC16A3/MCT4) is one of the membrane protein stubs in cells that is structurally able to output lactic and pyruvic acids and affect the acidity of the tumor microenvironments. [15][16][17] High expression of MCT4 has been reported to be a biomarker in various types of tumors, [18][19][20][21][22][23][24] which makes it an appealing therapeutic target in cancers. The blockade of MCT4 expression has been shown to represent a novel treatment target in glioblastoma, large B-cell lymphoma, and multiple myeloma.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma

Long

Gao

et al. 2018

Cancer Medicine

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Monocarboxylate transporter‐4 (MCT4), a monocarboxylic acid transporter, demonstrates significantly increased expression in the majority of malignancies. We performed an experiment using BALB/C mice, and our results showed that ShMCT4 transfection or the pharmaceutic inhibition of MCT4 with 7acc1 strengthens the activity of NK cells. The results of a calcein assay revealed that the cytotoxicity of NK cells was strengthened via inhibition of MCT4. In addition, ELISA testing showed that the content of perforin and CD107a was increased, and PCR amplification and immunoblotting revealed that the expression of NKG2D and H60 was upregulated after the inhibition of MCT4. Further, we observed an elevated pH value, decreased extracellular lactate flow, and attenuated tumor growth. Therefore, we concluded that the inhibition of MCT4 enhanced the cytotoxicity of NK cells by blocking lactate flux and reversing the acidified tumor microenvironment. In addition to these findings, we also discovered that MCT4 depletion may have a pronounced impact on autophagy, which was surmised by observing that the inhibition of autophagy (3MA) pulled the enhanced cytotoxicity of NK cells downwards. Together, these data suggest that the key effect of MCT4 depletion on NK cells probably utilizes inductive autophagy as a compensatory metabolic mechanism to minimize the acidic extracellular microenvironment associated with lactate export in tumors.

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Evaluation of MCT1, MCT4 and CD147 Genes in Peripheral Blood Cells of Breast Cancer Patients and Their Potential Use as Diagnostic and Prognostic Markers

Cited by 17 publications

References 37 publications

Clinicopathological and prognostic involvements of MCT1, MCT4 and IL7R in esophageal squamous cell carcinoma

Clinicopathological and prognostic involvements of MCT1, MCT4 and IL7R in esophageal squamous cell carcinoma

Clinicopathological and prognostic involvements of MCT1, MCT4 and IL-7R in esophageal squamous cell carcinoma

Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma

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