Prognostic significance of monocarboxylate transporter expression in oral cavity tumors

Simões-Sousa, Susana; Granja, Sara; Pinheiro, Céline; Fernandes, Daniela; Longatto‐Filho, Adhemar; Laus, Ana Carolina; Alves, Cira Danielle Casado; Suárez-Peñaranda, José Manuel; Pérez‐Sayáns, Mario; Carvalho, André L.; Schmitt, Fernando; García‐García, Abel; Baltazar, Fátima

doi:10.1080/15384101.2016.1188239

Cited by 41 publications

(43 citation statements)

References 66 publications

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“…Understanding the role of these transporters in tumours will clarify their contribution to tumour metabolism and the malignant phenotype. Recent efforts have been made to identify the prognostic significance of MCT1 [ 14 , 15 , 21 , 23 , 24 , 34 ] and MCT4 (reviewed by [ 36 ]) in different tumour types, however none have studied their role in EC.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, MCT4 (efflux of lactate) and MCT1 (both influx and efflux of lactate) are among the most important regulators of intracellular pH homeostasis in tumours and other high glycolytic tissues [ 10 , 11 ]. Upregulation of MCTs has been shown in many malignancies including colorectal [ 12 , 13 ], cervix [ 14 ], breast [ 15 , 16 ], prostate [ 17 ], central nervous system [ 18 , 19 ], soft tissue [ 20 ], gastrointestinal [ 21 , 22 ], oral cavity [ 23 ], urothelial [ 24 ] and lung carcinomas [ 25 ] and high expression is associated with poor prognosis. Both MCT1 and 4 require association with the ancillary protein CD147 (also known as EMMPRIN or Basigin) for plasma membrane expression and activity [ 26 – 28 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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BackgroundEndometrial cancer (EC) is a major health concern due to its rising incidence. Whilst early stage disease is generally cured by surgery, advanced EC has a poor prognosis with limited treatment options. Altered energy metabolism is a hallmark of malignancy. Cancer cells drive tumour growth through aerobic glycolysis and must export lactate to maintain intracellular pH. The aim of this study was to evaluate the expression of the lactate/proton monocarboxylate transporters MCT1 and MCT4 and their chaperone CD147 in EC, with the ultimate aim of directing future drug development.MethodsMCT1, MCT4 and CD147 expression was examined using immunohistochemical analysis in 90 endometrial tumours and correlated with clinico-pathological characteristics and survival outcomes.ResultsMCT1 and MCT4 expression was observed in the cytoplasm, the plasma membrane or both locations. CD147 was detected in the plasma membrane and associated with MCT1 (p = 0.003) but not with MCT4 (p = 0.207) expression. High MCT1 expression was associated with reduced overall survival (p = 0.029) and remained statistically significant after adjustment for survival covariates (p = 0.017).ConclusionOur data suggest that MCT1 expression is an important marker of poor prognosis in EC. MCT1 inhibition may have potential as a treatment for advanced or recurrent EC.Electronic supplementary materialThe online version of this article (10.1186/s12907-017-0067-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…The MCT family consists of fourteen members [29,30]; MCT4 is the only member with H + -dependent transporters of monocarboxylic acids [31,32]. Increasing reports show that expression of MCT4 has also been linked to poor prognosis in several cancers [33,34]. Malignant tumors overexpress MCT4, characteristic of metastatic cancer in association with HIF-1α upregulation [35,36].…”

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confidence: 99%

Monocarboxylate Transporter 4 Regulates Glioblastoma Motility and Monocyte Binding Ability

Lai

Lin

Liu

et al. 2020

Cancers

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Glioblastoma (GBM) is characterized by severe hypoxic and acidic stress in an abnormal microenvironment. Monocarboxylate transporter (MCT)4, a pH-regulating protein, plays an important role in pH homeostasis of the glycolytic metabolic pathways in cancer cells. The present study showed that GBM exposure to hypoxic conditions increased MCT4 expression. We further analyzed the glioma patient database and found that MCT4 was significantly overexpressed in patients with GBM, and the MCT4 levels positively correlated with the clinico-pathological grades of gliomas. We further found that MCT4 knockdown abolished the hypoxia-enhanced of GBM cell motility and monocyte adhesion. However, the overexpression of MCT4 promoted GBM cell migration and monocyte adhesion activity. Our results also revealed that MCT4-regulated GBM cell motility and monocyte adhesion are mediated by activation of the serine/threonine-specific protein kinase (AKT), focal adhesion kinase (FAK), and epidermal growth factor receptor (EGFR) signaling pathways. Moreover, hypoxia mediated the acetylated signal transducer and activator of transcription (STAT)3 expression and regulated the transcriptional activity of hypoxia inducible factor (HIF)-1α in GBM cell lines. In a GBM mouse model, MCT4 was significantly increased in the tumor necrotic tissues. These findings raise the possibility for the development of novel therapeutic strategies targeting MCT4.

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“…For that reason, the role of MCTs in several cancer types, including expression analysis in human cancer tissues have been widely explored in the past years (for an extensive review see [16]). MCT1 and MCT4 are upregulated in tumour cells when compared to adjacent normal tissue in a variety of human malignancies including lung [17], breast [18], head and neck [19], renal [20], brain [21], adrenal [22], melanomas [23], pancreatic [24], colorectal [25], ovarian [26], bladder [27] and cervix [28]. Interestingly, in liver and prostate cancer, MCT1 appears downregulated, while MCT4 is upregulated [29,30].…”

Section: Expression and Prognostic Value Of Mctsmentioning

confidence: 99%

“…Diverse immunohistochemical studies have reported CAIX to be expressed in several cancers, including malignancies of the breast [167,168], colon/rectum, head and neck [19,169], lung [170], brain [171], bladder [172], ovarian [173], and kidney [166] (for review see [174]). Importantly, its expression is scarce in normal human tissues, being only detected in the gastrointestinal tract [175].…”

Section: Expression and Prognostic Value Of Casmentioning

confidence: 99%

Value of pH regulators in the diagnosis, prognosis and treatment of cancer

Granja

Tavares-Valente

Queirós

et al. 2017

Seminars in Cancer Biology

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Altered metabolism, associated with acidification of the extracellular milieu, is one of the major features of cancer. As pH regulation is crucial for the maintenance of all biological functions, cancer cells rely on the activity of lactate exporters and proton transporters to regulate their intracellular pH. The major players in cancer pH regulation are proton pump ATPases, sodium-proton exchangers (NHEs), monocarboxylate transporters (MCTs), carbonic anhydrases (CAs) and anion exchangers (AEs), which have been shown to be upregulated in several human malignancies. Thanks to the activity of the proton pumps and transporters, tumours acidify their microenvironment, becoming more aggressive and resistant to therapy. Thus, targeting tumour pH may contribute to more effective anticancer strategies for controlling tumour progression and therapeutic resistance. In the present study, we review the role of the main pH regulators expressed in human cancer cells, including their diagnostic and prognostic value, as well as their usefulness as therapeutic targets.

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Prognostic significance of monocarboxylate transporter expression in oral cavity tumors

Abstract: Overexpression of MCT1/4, CD147, GLUT1 and CAIX, supports previous findings of metabolic reprograming in OCC, warranting future studies to explore the hyper-glycolytic phenotype of these tumors. Importantly, MCT expression revealed to have a prognostic value in OCC survival.

Cited by 41 publications

References 66 publications

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

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

Monocarboxylate Transporter 4 Regulates Glioblastoma Motility and Monocyte Binding Ability

Value of pH regulators in the diagnosis, prognosis and treatment of cancer

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