Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer

Latif, Ayşe; Chadwick, Amy L.; Kitson, Sarah; Gregson, Hannah J.; Sivalingam, Vanitha N.; Bolton, James M.; McVey, Rhona J; Roberts, Stephen A; Marshall, Kay; Williams, Kaye J.; Stratford, Ian J.; Crosbie, Emma J.

doi:10.1186/s12907-017-0067-7

Cited by 40 publications

(30 citation statements)

References 47 publications

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“…Both MCT1 and MCT4 expression were obviously associated with higher HRs, indicating poor prognosis. The relationship was stronger for MCT4 despite the significant heterogeneity between studies (HR=1.70, 95%CI=1.19-2.42, P=0.003, I 2 =71%) while the relationship in two studies 30,37 reporting their HRs for DFS in solid tumours was less apparent (HR=1.48, 95%CI=1.04-2.10, P=0.03, I 2 =0%, Figure 3C and D).…”

Section: Resultsmentioning

confidence: 92%

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MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis

Javaeed¹,

Ghauri²

2019

Oncol Rev

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The role of several metabolic changes, such as hypoxia and acidosis, in the tumour environment has caught the attention of researchers in cancer progression and invasion. Lactate transport is one of the acidosis-enhancing processes that are mediated via monocarboxylate transporters (MCTs). We conducted a systematic review and meta-analysis to investigate the expression of two cancer-relevant MCTs (MCT1 and MCT4) and their potential prognostic significance in patients with metastasis of different types of cancer. Studies were included if they reported the number of metastatic tissue samples expressing either low or high levels of MCT1 and/or MCT4 or those revealing the hazard ratios (HRs) of the overall survival (OS) or disease-free survival (DFS) as prognostic indicators. During the period between 2010 and 2018, a total of 20 articles including 3831 patients (56.3% males) were identified. There was a significant association between MCT4 expression (high versus low) and lymph node metastasis [odds ratio (OR)=1.87, 95% confidence interval (CI)=1.10-3.17, P=0.02] and distant metastasis (OR=2.18, 95%CI=1.65-2.86, P<0.001) and the correlation remained significant for colorectal and hepatic cancer in subgroup analysis. For survival analysis, patients with shorter OS periods exhibited a higher MCT4 expression [hazard ratio (HR)=1.78, 95%CI=1.49-2.13, P<0.001], while DFS was shorter in patients with high MCT1 (HR=1.48, 95%CI=1.04-2.10, P=0.03) and MCT4 expression (HR=1.70, 95%CI=1.19-2.42, P=0.003) when compared to their counterparts with low expression levels. Future research studies should consider the pharmacologic inhibition of MCT4 to effectively inhibit cancer progression to metastasis.

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Section: Resultsmentioning

confidence: 92%

“…There was a significant heterogeneity between a total of 9 studies 19,20,27,29,32-34,36,37 that demonstrated LNM with the expression of MCT1 and MCT4 (I 2 =77% and 63%, respectively). Interestingly, there was a significant association between MCT4 expression (high versus low) and LNM (OR=1.87, 95%CI=1.10– 3.17, P=0.02, Figure 2B).…”

Section: Resultsmentioning

confidence: 99%

MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis

Javaeed¹,

Ghauri²

2019

Oncol Rev

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“…In fact, a comparison of healthy and cancerous cell lines suggested that SLC proteins have greater changes in their coexpression networks than protein kinases [28]. Proteins like SLC2A1, SLC39A14, and SLC16A1 may serve as prognostic biomarkers in cancers due to their central role in the development of cancer and responses to treatments [551][552][553]. Thus, it is imperative to continue studying transport proteins in a comprehensive manner, focusing not only on individual transport functions, but also unraveling the complex relationships between different transporters and metabolic states.…”

Section: Discussionmentioning

confidence: 99%

A guide to plasma membrane solute carrier proteins

2020

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This review aims to serve as an introduction to the solute carrier proteins (SLC) superfamily of transporter proteins and their roles in human cells. The SLC superfamily currently includes 458 transport proteins in 65 families that carry a wide variety of substances across cellular membranes. While members of this superfamily are found throughout cellular organelles, this review focuses on transporters expressed at the plasma membrane. At the cell surface, SLC proteins may be viewed as gatekeepers of the cellular milieu, dynamically responding to different metabolic states. With altered metabolism being one of the hallmarks of cancer, we also briefly review the roles that surface SLC proteins play in the development and progression of cancer through their influence on regulating metabolism and environmental conditions.

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“…Monocarboxylate Transporter 1 (MCT1) is an important protein for lactic acid and pyruvate uptake by cells, while MCT4 is an important protein for cell transport of lactic acid and pyruvate, which play an important role in regulating lactic acid metabolism. It has been reported that MCT1 was an independent prognostic biomarker in endometrial cancer (99). A recent study reported that the use of monocarboxylic acid transporter (MCT) inhibitors can reverse the inhibition of lactic acid on macrophage lysosomes (100).…”

Section: Type 2 Diabetes and Endometrial Cancermentioning

confidence: 99%

The Role of Metabolic Syndrome in Endometrial Cancer: A Review

2019

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Endometrial cancer is one of the most common cancers of the female reproductive system. Although surgery, radiotherapy, chemotherapy, and hormone therapy can significantly improve the survival of patients, the treatment of patients with very early lesions and a strong desire to retain reproductive function or late recurrence is still in the early stages. Metabolic syndrome (MS) is a clustering of at least three of the five following medical conditions: central obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Obesity, diabetes and hypertension often coexist in patients with endometrial cancer, which increases the risk of endometrial cancer, also known as the “triple syndrome of endometrial cancer.” In recent years, epidemiological and clinical studies have found that MS associated with metabolic diseases is closely related to the incidence of endometrial cancer. However, the key molecular mechanisms underlying the induction of endometrial cancer by MS have not been elucidated to date. Characterizing the tumor metabolism microenvironment will be advantageous for achieving a comprehensive view of the molecular mechanism of metabolic syndrome associated with endometrial cancer and for providing a new target for the treatment of endometrial cancer. This review focuses on recent advances in determining the role of metabolic syndrome-related factors and mechanisms in the pathogenesis of endometrial cancer. We suggest that interfering with the tumor metabolic microenvironment-related molecular signals may inhibit the occurrence of endometrial cancer.

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Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer

Cited by 40 publications

References 47 publications

MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis

MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis

A guide to plasma membrane solute carrier proteins

The Role of Metabolic Syndrome in Endometrial Cancer: A Review

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