Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review

Silva, Ana; Cerqueira, Mónica Costa; Rosa, B.; Sobral, Catarina; Pinto-Ribeiro, Filipa; Costa, Marta; Baltazar, Fátima; Afonso, José António

doi:10.3390/ijms24065141

Cited by 10 publications

(7 citation statements)

References 89 publications

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“…MCT1, a bi-directional proton-mediated shuttle protein, can serve as a possible biomarker of poor prognosis in different types of cancers [ 22 ]. MCT1 is overexpressed in bladder cancer and has been strongly associated with the maintenance of the glycolytic phenotype of tumors and with cisplatin resistance [ 14 , 15 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Lactate Transport Inhibition by AZD3965 in Muscle-Invasive Urothelial Bladder Cancer

Silva,

Félix,

Cerqueira

et al. 2023

Pharmaceutics

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The Warburg Effect is characterized by high rates of glucose uptake and lactate production. Monocarboxylate transporters (MCTs) are crucial to avoid cellular acidosis by internal lactate accumulation, being largely overexpressed by cancer cells and associated with cancer aggressiveness. The MCT1-specific inhibitor AZD3965 has shown encouraging results in different cancer models. However, it has not been tested in urothelial bladder cancer (UBC), a neoplasm where rates of recurrence, progression and platinum-based resistance are generally elevated. We used two muscle-invasive UBC cell lines to study AZD3965 activity regarding lactate production, UBC cells’ viability and proliferation, cell cycle profile, and migration and invasion properties. An “in vivo” assay with the chick chorioallantoic membrane model was additionally performed, as well as the combination of the compound with cisplatin. AZD3965 demonstrated anticancer activity upon low levels of MCT4, while a general lack of sensitivity was observed under MCT4 high expression. Cell viability, proliferation and migration were reduced, cell cycle was arrested, and tumor growth “in vivo” was inhibited. The compound sensitized these MCT4-low-expressing cells to cisplatin. Thus, AZD3965 seems to display anticancer properties in UBC under a low MCT4-expression setting, but additional studies are necessary to confirm AZD3965 activity in this cancer model.

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Section: Introductionmentioning

confidence: 99%

Effects of Lactate Transport Inhibition by AZD3965 in Muscle-Invasive Urothelial Bladder Cancer

Silva,

Félix,

Cerqueira

et al. 2023

Pharmaceutics

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“…LINC02594, also known as CTC-501O10.1, exhibits up-regulation in the plasma of patients diagnosed with gastric cancer and thus holds potential as a biomarker for detecting this malignancy [ 58 ]. AL357055.3(lnc-SLC16A1-2:1) has not been reported, but its homologous protein SLC16A1 is a confirmed poor prognosis marker in various malignant tumors, possibly due to its involvement in glycolysis and glucose metabolism synthesis [ 59 , 60 ]. AL355974.3, also referred to as lnc-COL4A1-7:1 in the human non-coding RNA library, lacks functional characterization in existing literature.…”

Section: Discussionmentioning

confidence: 99%

PD-L1-related IncRNAs are associated with malignant characteristics and immune microenvironment in glioma

Xia,

Tu,

Liu

et al. 2023

Aging

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Background: The expression of long non-coding RNA (lncRNA) can function as diagnostic and therapeutic biomarker for tumors. This research explores the role of PD-L1-related lncRNAs in affecting malignant characteristics and the immune microenvironment of glioma. Methods: Downloading gene expression profiles and clinicopathological information of glioma from TCGA and CGGA databases, 6 PD-L1-related lncRNAs were identified through correlation analysis, Cox and LASSO regression analysis, establishing the risk score model based on them. Bioinformatics analysis and cell experiments in vitro were adopted to verify the effects of LINC01271 on glioma. Results: Risk scores based on 6 PD-L1-related lncRNAs (AL355974.3, LINC01271, AC011899.3, MIR4500HG, LINC02594, AL357055.3) can reflect malignant characteristics and immunotherapy response of glioma. Patients with high LINC01271 expression had a worse prognosis, a higher abundance of M1 subtype macrophages in the immune microenvironment, and a higher degree of tumor malignancy. Experiments in vitro confirmed its positive regulatory effect on the proliferation and migration of glioma cells. Conclusions: The risk score model based on 6 PD-L1-related lncRNAs can reflect the malignant characteristics and prognosis of glioma. LINC01271 can independently be used as a new target for prognosis evaluation and therapy.

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“…MCTs are over-expressed in many tumors, such as breast [61][62][63], colorectal [64][65][66], prostate [67][68][69], lung [70,71], esophageal [72,73], small cell lung [74], ovarian [75], gastric [76][77][78], endometrial [79], renal [80][81][82], hepatic [83,84], pancreatic [85][86][87] cancers, leukemia [88,89], lymphoma [90][91][92], head and neck squamous cell cancer [93][94][95], glioma [96], soft tissue sarcoma [97], and testicular germ cell tumors [98]. In summary, all kinds of tumors express MCT1-4, and in all of them, they play a role in malignant progression [99,100].…”

Section: Mctsmentioning

confidence: 99%

Exploring monocarboxylate transporter inhibition for cancer treatment

Koltai,

Fliegel

2024

Exploration of Targeted Anti-Tumor Therapy

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Cells are separated from the environment by a lipid bilayer membrane that is relatively impermeable to solutes. The transport of ions and small molecules across this membrane is an essential process in cell biology and metabolism. Monocarboxylate transporters (MCTs) belong to a vast family of solute carriers (SLCs) that facilitate the transport of certain hydrophylic small compounds through the bilipid cell membrane. The existence of 446 genes that code for SLCs is the best evidence of their importance. In-depth research on MCTs is quite recent and probably promoted by their role in cancer development and progression. Importantly, it has recently been realized that these transporters represent an interesting target for cancer treatment. The search for clinically useful monocarboxylate inhibitors is an even more recent field. There is limited pre-clinical and clinical experience with new inhibitors and their precise mechanism of action is still under investigation. What is common to all of them is the inhibition of lactate transport. This review discusses the structure and function of MCTs, their participation in cancer, and old and newly developed inhibitors. Some suggestions on how to improve their anticancer effects are also discussed.

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Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review

Cited by 10 publications

References 89 publications

Effects of Lactate Transport Inhibition by AZD3965 in Muscle-Invasive Urothelial Bladder Cancer

Effects of Lactate Transport Inhibition by AZD3965 in Muscle-Invasive Urothelial Bladder Cancer

PD-L1-related IncRNAs are associated with malignant characteristics and immune microenvironment in glioma

Exploring monocarboxylate transporter inhibition for cancer treatment

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