Metabolic Reprogramming of Thyroid Cancer Cells and Crosstalk in Their Microenvironment

Bao, Lisha; Xu, Tong; Lu, Xixuan; Huang, Ping; Pan, Zongfu; Ge, Minghua

doi:10.3389/fonc.2021.773028

Cited by 16 publications

(12 citation statements)

References 188 publications

(216 reference statements)

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“…Therefore, the producing cell of abnormal metabolites requires further evaluation by more in-depth studies. With the accumulation of abnormal metabolites in TME, it will inhibit T cell function ( 32 ), lead to the reprogramming of multiple metabolic pathways in MM ( 33 ), which is conducive to the formation and progression of tumors ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Serum Abnormal Metabolites for Evaluating Therapeutic Response and Prognosis of Patients With Multiple Myeloma

et al. 2022

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AimsTo evaluate abnormal metabolites related to treatment response and prognosis of multiple myeloma (MM) patients through ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS).MethodsForty-six symptomatic MM patients were included in this study who had a prior high level of positive monoclonal proteins before receiving targeted therapy with bortezomib-based regimens. UPLC-MS along with traditional immunofixation was performed on MM diagnostic samples and effective serum samples, and UPLC-MS was used to target valuable metabolic markers related to M protein.MM patients were segregated into pre-therapy (pre-T) and post-therapy (post-T) groups according to the response after chemotherapy. A monoclonal protein could be detected at baseline in 33 newly diagnosed MM (NDMM), 13 refractory and relapsed MM (RRMM) patients and 20 healthy controls (HC) by immunofixation.ResultsBetween pre-T and post-T patients, the data showed that 32, 28 and 3 different metabolites were significantly correlated with M protein in IgG, IgA and light chain-type MM, respectively. These identified metabolites were significantly enriched in arginine and proline metabolism as well as glycerophospholipid metabolism pathways. Among them, PC (19:0/22:2) was displayed to increase significantly and consistently with M protein in each subtype of MM after treatment, which obviously indicated that it was related to the treatment response of MM. Further survival analysis of metabolic markers found that aspartic acid, LysoPE (16:0), SM (d18:1/17:0), PC (18:0/24:1), PC (16:0/16:0), TG (18:1/18:1/22:5) and LysoPE (18:2) reaching a certain cutoff value may be associated with shorter progression free survival (PFS). Finally, Cox multivariate regression analysis identified three factors were independent prognostic factors of MM. Moreover, there were significantly different in PC (19:0/22:2) and in aspartic acid between MM patients and healthy people.ConclusionThis work identified significant metabolic disorders in 46 pairs off pre- and post-therapy MM patients, specifically in arginine, proline and glycerophospholipid pathways. The abnormal metabolites have the potential to serve as new biomarkers for evaluating treatment response and prognosis, as well as early monitoring of disease activity. Therefore, these systematic studies on abnormal metabolites as biomarkers for diagnosis and treatment will provide the evidence for future precise treatment of MM.

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Section: Discussionmentioning

confidence: 99%

Serum Abnormal Metabolites for Evaluating Therapeutic Response and Prognosis of Patients With Multiple Myeloma

et al. 2022

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“…Among multiple mechanisms, the increase in D2-derived T3 in ATC may support the increased energy consumption consequent to its highly proliferative state. In such situation, cancer cells enhance the aerobic glycolysis as a source of ATP for the increased energy request (Bao et al, 2021). Notably, T3 increases the expression of glycolytic genes (such as aldolase A, enolase, pyruvate kinase M2 and lactate dehydrogenase A) (Miro et al, 2021), as well as the glucose transporter genes GLUT1, 3 and 4 (Casla et al, 1990).…”

Section: Anaplastic Thyroid Cancer Expresses D2mentioning

confidence: 99%

Deiodinases in thyroid tumorigenesis

Stefano

Porcelli

Schlumberger

et al. 2023

Endocrine-Related Cancer

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The three deiodinase selenoenzymes are key regulators of intracellular thyroid hormone (TH) levels. The two TH-activating deiodinases (D1 and D2) are normally expressed in follicular thyroid cells and contribute to the overall TH production. During thyroid tumorigenesis, the deiodinase expression profile changes to customize intracellular TH levels to different requirements of cancer cells. Differentiated thyroid cancers overexpress the TH-inactivating D3, likely to reduce the TH signaling within the tumor. Strikingly, recent evidences suggest that during the late-stage of thyroid tumorigenesis D2 expression raises and this, together with a reduction in D3 expression levels, increases TH intracellular signaling in dedifferentiated thyroid cancers. These findings call into question the different function of TH on the various stages of thyroid cancers.

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“…Besides elevated rate of glycolysis, cancer cells undergo complex metabolic reprogramming, including increased glutamine consumption and enhanced anabolism. TME cells are also featured by active metabolism, resulting in the suppression of antitumor immune response [ 72 ]. Cancer metabolic networks control not only energy balance and growth of tumor cells but are also important modulators of epigenetic mechanisms [ 71 ].…”

Section: Implication Of Mirnas In Carcinogenesis and Leukemogenesismentioning

confidence: 99%

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

Gaál

2022

IJMS

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MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs, that are involved in the multistep process of carcinogenesis, contributing to all established hallmarks of cancer. In this review, implications of miRNAs in hematological malignancies and their clinical utilization fields are discussed. As components of the complex regulatory network of gene expression, influenced by the tissue microenvironment and epigenetic modifiers, miRNAs are “micromanagers” of all physiological processes including the regulation of hematopoiesis and metabolic pathways. Dysregulated miRNA expression levels contribute to both the initiation and progression of acute leukemias, the metabolic reprogramming of malignantly transformed hematopoietic precursors, and to the development of chemoresistance. Since they are highly stable and can be easily quantified in body fluids and tissue specimens, miRNAs are promising biomarkers for the early detection of hematological malignancies. Besides novel opportunities for differential diagnosis, miRNAs can contribute to advanced chemoresistance prediction and prognostic stratification of acute leukemias. Synthetic oligonucleotides and delivery vehicles aim the therapeutic modulation of miRNA expression levels. However, major challenges such as efficient delivery to specific locations, differences of miRNA expression patterns between pediatric and adult hematological malignancies, and potential side effects of miRNA-based therapies should be considered.

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Metabolic Reprogramming of Thyroid Cancer Cells and Crosstalk in Their Microenvironment

Cited by 16 publications

References 188 publications

Serum Abnormal Metabolites for Evaluating Therapeutic Response and Prognosis of Patients With Multiple Myeloma

Serum Abnormal Metabolites for Evaluating Therapeutic Response and Prognosis of Patients With Multiple Myeloma

Deiodinases in thyroid tumorigenesis

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

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