scholarly journals Effect of monocarboxylate transporter-1 on the biological behavior of iodine-refractory thyroid carcinoma

2021 ◽  
Vol 10 (11) ◽  
pp. 4914-4928
Author(s):  
Qian Li ◽  
Bin Xu ◽  
Yunxiang Tang ◽  
Yuxia Li ◽  
Hong Ying
Keyword(s):  
Thyroid Carcinoma ◽  
Monocarboxylate Transporter ◽  
Biological Behavior ◽  
Monocarboxylate Transporter 1

Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs

2019 ◽  
Vol 19 (1) ◽  
pp. 51-78 ◽  
Author(s):  
Ota Fuchs
Keyword(s):  
Clinical Trials ◽  
Transcription Factors ◽  
Ubiquitin Ligase ◽  
Mononuclear Cells ◽  
E3 Ubiquitin Ligase ◽  
Lymphocytic Leukemia ◽  
Monocarboxylate Transporter ◽  
Immunomodulatory Drugs ◽  
Monocarboxylate Transporter 1 ◽  
Argonaute 2

Thalidomide and its derivatives (lenalidomide, pomalidomide, avadomide, iberdomide hydrochoride, CC-885 and CC-90009) form the family of immunomodulatory drugs (IMiDs). Lenalidomide (CC5013, Revlimid®) was approved by the US FDA and the EMA for the treatment of multiple myeloma (MM) patients, low or intermediate-1 risk transfusion-dependent myelodysplastic syndrome (MDS) with chromosome 5q deletion [del(5q)] and relapsed and/or refractory mantle cell lymphoma following bortezomib. Lenalidomide has also been studied in clinical trials and has shown promising activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Lenalidomide has anti-inflammatory effects and inhibits angiogenesis. Pomalidomide (CC4047, Imnovid® [EU], Pomalyst® [USA]) was approved for advanced MM insensitive to bortezomib and lenalidomide. Other IMiDs are in phases 1 and 2 of clinical trials. Cereblon (CRBN) seems to have an important role in IMiDs action in both lymphoid and myeloid hematological malignancies. Cereblon acts as the substrate receptor of a cullin-4 really interesting new gene (RING) E3 ubiquitin ligase CRL4CRBN. This E3 ubiquitin ligase in the absence of lenalidomide ubiquitinates CRBN itself and the other components of CRL4CRBN complex. Presence of lenalidomide changes specificity of CRL4CRBN which ubiquitinates two transcription factors, IKZF1 (Ikaros) and IKZF3 (Aiolos), and casein kinase 1α (CK1α) and marks them for degradation in proteasomes. Both these transcription factors (IKZF1 and IKZF3) stimulate proliferation of MM cells and inhibit T cells. Low CRBN level was connected with insensitivity of MM cells to lenalidomide. Lenalidomide decreases expression of protein argonaute-2, which binds to cereblon. Argonaute-2 seems to be an important drug target against IMiDs resistance in MM cells. Lenalidomide decreases also basigin and monocarboxylate transporter 1 in MM cells. MM cells with low expression of Ikaros, Aiolos and basigin are more sensitive to lenalidomide treatment. The CK1α gene (CSNK1A1) is located on 5q32 in commonly deleted region (CDR) in del(5q) MDS. Inhibition of CK1α sensitizes del(5q) MDS cells to lenalidomide. CK1α mediates also survival of malignant plasma cells in MM. Though, inhibition of CK1α is a potential novel therapy not only in del(5q) MDS but also in MM. High level of full length CRBN mRNA in mononuclear cells of bone marrow and of peripheral blood seems to be necessary for successful therapy of del(5q) MDS with lenalidomide. While transfusion independence (TI) after lenalidomide treatment is more than 60% in MDS patients with del(5q), only 25% TI and substantially shorter duration of response with occurrence of neutropenia and thrombocytopenia were achieved in lower risk MDS patients with normal karyotype treated with lenalidomide. Shortage of the biomarkers for lenalidomide response in these MDS patients is the main problem up to now.

scholarly journals Monocarboxylate transporter-1 (MCT1) protein expression in head and neck cancer affects clinical outcome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Martin Leu ◽  
J. Kitz ◽  
Y. Pilavakis ◽  
S. Hakroush ◽  
H. A. Wolff ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Protein Expression ◽  
Head And Neck ◽  
Cox Regression ◽  
Locally Advanced ◽  
Monocarboxylate Transporter ◽  
Positive Staining ◽  
Monocarboxylate Transporter 1 ◽  
Prognostic Features ◽  
Hpv Status

AbstractTreatment of locally advanced, unresectable head and neck squamous cell carcinoma (HNSCC) often yields only modest results with radiochemotherapy (RCT) as standard of care. Prognostic features related to outcome upon RCT might be highly valuable to improve treatment. Monocarboxylate transporters-1 and -4 (MCT1/MCT4) were evaluated as potential biomarkers. A cohort of HNSCC patients without signs for distant metastases was assessed eliciting 82 individuals eligible whereof 90% were diagnosed with locally advanced stage IV. Tumor specimens were stained for MCT1 and MCT4 in the cell membrane by immunohistochemistry. Obtained data were evaluated with respect to overall (OS) and progression-free survival (PFS). Protein expression of MCT1 and MCT4 in cell membrane was detected in 16% and 85% of the tumors, respectively. Expression of both transporters was not statistically different according to the human papilloma virus (HPV) status. Positive staining for MCT1 (n = 13, negative in n = 69) strongly worsened PFS with a hazard ratio (HR) of 3.1 (95%-confidence interval 1.6–5.7, p < 0.001). OS was likewise affected with a HR of 3.8 (2.0–7.3, p < 0.001). Multivariable Cox regression confirmed these findings. We propose MCT1 as a promising biomarker in HNSCC treated by primary RCT.

scholarly journals Synthesis and radiofluorination of [18F]F-BAY-8002: a novel potential radiotracer for PET imaging of monocarboxylate transporter 1

2021 ◽  
Vol 96-97 ◽  
pp. S74-S75
Author(s):  
Masoud Sadeghzadeh ◽  
Barbara Wenzel ◽  
Friedrich-Alexander Ludwig ◽  
Klaus Kopka ◽  
Rares Moldovan ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Monocarboxylate Transporter ◽  
Monocarboxylate Transporter 1

scholarly journals Monocarboxylate transporter 1 blockade with AZD3965 inhibits lipid biosynthesis and increases tumour immune cell infiltration

2020 ◽  
Vol 122 (6) ◽  
pp. 895-903 ◽  
Author(s):  
Mounia Beloueche-Babari ◽  
Teresa Casals Galobart ◽  
Teresa Delgado-Goni ◽  
Slawomir Wantuch ◽  
Harold G. Parkes ◽  
...  
Keyword(s):  
Immune Cell ◽  
Lipid Biosynthesis ◽  
Monocarboxylate Transporter ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Monocarboxylate Transporter 1

Monocarboxylate transporter 1 is up-regulated in Caco-2 cells by the methionine precursor DL-2-hydroxy-(4-methylthio)butanoic acid

2014 ◽  
Vol 202 (3) ◽  
pp. 555-560 ◽  
Author(s):  
Raquel Martín-Venegas ◽  
M.Teresa Brufau ◽  
Oriol Mañas-Cano ◽  
Yves Mercier ◽  
Magalie K. Nonis ◽  
...  
Keyword(s):  
Monocarboxylate Transporter ◽  
Butanoic Acid ◽  
Monocarboxylate Transporter 1

scholarly journals Comparison of Lactate Transport in Astroglial Cells and Monocarboxylate Transporter 1 (MCT 1) ExpressingXenopus laevisOocytes

1997 ◽  
Vol 272 (48) ◽  
pp. 30096-30102 ◽  
Author(s):  
Stefan Bröer ◽  
Basim Rahman ◽  
Gioranni Pellegri ◽  
Luc Pellerin ◽  
Jean-Luc Martin ◽  
...  
Keyword(s):  
Monocarboxylate Transporter ◽  
Lactate Transport ◽  
Astroglial Cells ◽  
Monocarboxylate Transporter 1

scholarly journals miR-124 Suppresses Pancreatic Ductal Adenocarcinoma Growth by Regulating Monocarboxylate Transporter 1-Mediated Cancer Lactate Metabolism

2018 ◽  
Vol 50 (3) ◽  
pp. 924-935 ◽  
Author(s):  
De-Hai Wu ◽  
Hao Liang ◽  
Shou-Nan Lu ◽  
Hao Wang ◽  
Zhi-Lei Su ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Intracellular Ph ◽  
Molecular Mechanisms ◽  
Monocarboxylate Transporter ◽  
Human Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Luciferase Reporter ◽  
Lactate Metabolism ◽  
Rt Pcr ◽  
Monocarboxylate Transporter 1

Background/Aims: Increasing evidence shows that reprogramming of energy metabolism is a hallmark of cancer. Considering the emergence of microRNAs as crucial modulators of cancer, this study aimed to better understand the molecular mechanisms of miR-124 in regulating glycolysis in human pancreatic cancer. Methods: RT-PCR was used to investigate the expression of monocarboxylate transporters (MCTs) in pancreatic ductal adenocarcinoma (PDAC) patient samples and the PANC-1 cell line. A public database and immunochemistry were used for comprehensive analysis of MCT1 expression. The targeting of MCT1 by miR-124 was predicted by software and validated for the MCT1 3’-UTR by dual-luciferase reporter analysis. Cell proliferation, apoptosis, migration, xenografting, and the intracellular pH and L-lactate levels were assessed. Hypoxia-inducible factor-α (HIF-1α) and lactate dehydrogenase A (LDH-A) expression levels were determined by RT-PCR and western blotting. Results: MCT1 expression was higher in PDAC tissue than in normal tissue. Inhibition of MCT1 affected lactate metabolism, resulting in a higher intracellular pH and less proliferation of PANC-1 cells. MCT1 was the target gene of miR-124. In in vitro experiments, miR-124 inhibited the glycolytic activity of PANC-1 cells by targeting MCT1, further decreasing the tumor phenotype by increasing the intracellular pH through LDH-A and HIF-1α. In in vivo experiments, overexpression of miR-124 and silencing of MCT1 significantly inhibited tumor growth. Conclusion: miR-124 inhibits the progression of PANC-1 by targeting MCT1 in the lactate metabolic pathway. Our findings provide novel evidence for further functional studies of miR-124, which might be useful for future therapeutic approaches to PDAC.

scholarly journals Inhibition of Alternative Cancer Cell Metabolism of EGFR Mutated Non-Small Cell Lung Cancer Serves as a Potential Therapeutic Strategy

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 181 ◽  
Author(s):  
Chung-Yu Huang ◽  
Li-Han Hsu ◽  
Chung-Yeh Chen ◽  
Gee-Chen Chang ◽  
Hui-Wen Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Oxidative Phosphorylation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Monocarboxylate Transporter ◽  
Metabolic Flexibility ◽  
Small Cell Lung ◽  
Efficient Treatment ◽  
Monocarboxylate Transporter 1

Targeted therapy is an efficient treatment for patients with epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Therapeutic resistance invariably occurs in NSCLC patients. Many studies have focused on drug resistance mechanisms, but only a few have addressed the metabolic flexibility in drug-resistant NSCLC. In the present study, we found that during the developing resistance to tyrosine kinase inhibitor (TKI), TKI-resistant NSCLC cells acquired metabolic flexibility in that they switched from dependence on glycolysis to oxidative phosphorylation by substantially increasing the activity of the mitochondria. Concurrently, we found the predominant expression of monocarboxylate transporter 1 (MCT-1) in the TKI-resistant NSCLC cells was strongly increased in those cells that oxidized lactate. Thus, we hypothesized that inhibiting MCT-1 could represent a novel treatment strategy. We treated cells with the MCT-1 inhibitor AZD3965. We found a significant decrease in cell proliferation and cell motility in TKI-sensitive and TKI-resistant cells. Taken together, these results demonstrated that gefitinib-resistant NSCLC cells harbored higher mitochondrial bioenergetics and MCT-1 expression. These results implied that targeting mitochondrial oxidative phosphorylation proteins or MCT-1 could serve as potential treatments for both TKI-sensitive and –resistant non-small cell lung cancer.

Sign in / Sign up

Export Citation Format

Share Document