Monocarboxylate transporter 4 predicts poor prognosis in hepatocellular carcinoma and is associated with cell proliferation and migration

Gao, Heng; Ming, Zhao; Zhang, Yaojun; Zhou, Dong; Xu, Li; Li, Guang Bing; Chen, Min Shan; Liu, Jun

doi:10.1007/s00432-014-1888-8

Cited by 53 publications

(51 citation statements)

References 28 publications

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“…34 The lactate exporter MCT4, which is overexpressed in glycolytic tumor cells, is a promising candidate for cancer prognosis in various cancer entities, such as pancreatic cancer, 35 clear cell renal cell carcinoma, 29 or hepatocellular carcinoma. 36 A recent meta-analysis corroborates that increased MCT4 expression is linked to poor patient outcome across five different cancer entities. 37…”

Section: Wwwcts-journalcommentioning

confidence: 86%

“…In prostate cancer, MCT2 has been proposed as a biomarker for disease diagnosis, because the transporter is not expressed in normal prostate tissue, an increase in expression can be observed in adjacent non‐neoplastic tissue and strong MCT2 expression is found in primary prostate tumor tissue samples 34. The lactate exporter MCT4, which is overexpressed in glycolytic tumor cells, is a promising candidate for cancer prognosis in various cancer entities, such as pancreatic cancer,35 clear cell renal cell carcinoma,29 or hepatocellular carcinoma 36. A recent meta‐analysis corroborates that increased MCT4 expression is linked to poor patient outcome across five different cancer entities 37…”

Section: Mcts In Cancermentioning

confidence: 99%

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Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Fisel

Schaeffeler

Schwab

2018

Clinical Translational Sci

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The solute carrier (SLC) SLC16 gene family comprises 14 members and encodes for monocarboxylate transporters (MCTs), which mediate the absorption and distribution of monocarboxylic compounds across plasma membranes. As the knowledge about their physiological function, activity, and regulation increases, their involvement and contribution to cancer and other diseases become increasingly evident. Moreover, promising opportunities for therapeutic interventions by directly targeting their endogenous functions or by exploiting their ability to deliver drugs to specific organ sites emerge.

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Section: Wwwcts-journalcommentioning

confidence: 86%

Section: Mcts In Cancermentioning

confidence: 99%

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Fisel

Schaeffeler

Schwab

2018

Clinical Translational Sci

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“…The role of over-expressed MCT4 in HCC has been illustrated. It is associated with HCC progression and poor prognosis[48,49]. The latest study observed the reduced expression of MCT1 and MCT2 in HCC[50].…”

Section: Reprogramming Of Glucose Metabolism-related Enzymes and Tranmentioning

confidence: 99%

Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects

Shang

Wang

2016

WJG

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Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due to the difficulties in early diagnosis and the high level of tumor invasion, metastasis and recurrence. It is urgent to explore the underlying mechanism of HCC carcinogenesis and progression to find out the specific biomarkers for HCC early diagnosis and the promising target for HCC chemotherapy. Recently, the reprogramming of cancer metabolism has been identified as a hallmark of cancer. The shift from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in HCC meets the demands of rapid cell proliferation and offers a favorable microenvironment for tumor progression. Such metabolic reprogramming could be considered as a critical link between the different HCC genotypes and phenotypes. The regulation of metabolic reprogramming in cancer is complex and may occur via genetic mutations and epigenetic modulations including oncogenes, tumor suppressor genes, signaling pathways, noncoding RNAs, and glycolytic enzymes etc. Understanding the regulatory mechanisms of glycolysis in HCC may enrich our knowledge of hepatocellular carcinogenesis and provide important foundations in the search for novel diagnostic biomarkers and promising therapeutic targets for HCC.

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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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Monocarboxylate transporter 4 predicts poor prognosis in hepatocellular carcinoma and is associated with cell proliferation and migration

Cited by 53 publications

References 28 publications

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects

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

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