Characterization of monocarboxylate transporter activity in hepatocellular carcinoma

Alves, Venâncio Avancini Ferreira; Pinheiro, Céline; Morais-Santos, Filipa; Felipe-Silva, Aloísio; Longatto‐Filho, Adhemar; Baltazar, Fátima

doi:10.3748/wjg.v20.i33.11780

Cited by 33 publications

(25 citation statements)

References 28 publications

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“…18 Interestingly, MCT2 cytoplasmic expression has already been associated with variables related to a less aggressive profile of hepatocellular carcinomas. 44 In this study, we observed that MCT2 was significantly associated with well-differentiated tumors.…”

Section: Discussionmentioning

confidence: 60%

“…25 In the present study, there was no association between MCT4 and overall survival. Since MCT2 expression was associated with good prognostic variables in other types of cancers 34,44 and in contrast to MCT1 and MCT4, is mainly responsible for the uptake of monocarboxylates into cells, 18 we analyzed tumors that express both MCT1 and MCT4, as these are the isoforms correlated with the hyperglycolytic phenotype, and were negative for MCT2. Although we did not find any association with the different clinicopatological data, interestingly, we observed that MCT1 (C)/MCT4(C)/MCT2(¡) tumors have a shorter overall survival.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of monocarboxylate transporter expression in oral cavity tumors

et al. 2016

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Prognostic significance of monocarboxylate transporter expression in oral cavity tumors

et al. 2016

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“…In our institution, corpses are refrigerated and medical autopsies are performed as soon as all technical and legal procedures are addressed and resolved. Nevertheless, we sought to minimize the effects of autolytic changes by excluding samples with morphological features of poor preservation, specifically by examining vimentin staining (comparing to positive and negative controls) to assure that protein preservation was good enough to yield reliable immunohistochemical studies [34] .…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

Felipe-Silva¹,

Wakamatsu²,

Cirqueira³

et al. 2016

WJG

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AIM:To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC). METHODS:In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related RESULTS:Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (≥ 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin was strongly correlated with that of K19. CONCLUSION:Expression of K19, p53, ERK1, ERK2, vimentin and nuclear beta-catenin was related to highergrade markers, as opposed to expression/overexpression of EGFR, MET and caspase 3.

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“…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]. However, the data from another study showed that MCT1 was over-expressed in HCC cells which facilitates the lactate exporting and promotes HCC glycolysis[51].…”

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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Characterization of monocarboxylate transporter activity in hepatocellular carcinoma

Abstract: MCT4 and GLUT1 appear to play a role in HCC progression, while MCT2 is lost during progression and associated with better prognosis.

Cited by 33 publications

References 28 publications

Prognostic significance of monocarboxylate transporter expression in oral cavity tumors

Prognostic significance of monocarboxylate transporter expression in oral cavity tumors

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects

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