Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma

Addie, Ruben D.; Kostidis, Sarantos; Corver, Willem E.; Oosting, Jan; Aminzadeh-Gohari, Sepideh; Feichtinger, René G.; Kofler, Barbara; Aydemirli, Mehtap Derya; Giera, Martin; Morreau, Hans

doi:10.1038/s41598-020-66599-1

Cited by 12 publications

(18 citation statements)

References 72 publications

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“…TPC1 and Nthy-ori 3-1 cells exhibited comparably normal patterns of basal and maximal OCR in response to treatment with mitochondrial complex inhibitors, while TPC1 ρ0 cells showed extremely low basal OCR and no response to treatments, confirming normal and completely abolished mitochondrial function in the parental TPC1 and TPC1 ρ0 cells, respectively. XTC.UC1 cells exhibited an intermediate pattern, that is, lower basal OCR and partial response to mitochondrial inhibitors, data consistent with Addie et al 23 , indicating the ETC in XTC.UC1 cells being partially impaired. In contrast, another group has reported a slightly different data on mitochondrial function in XTC.UC1 cells, indicating almost complete abolishment of mitochondrial function 18 .…”

Section: Resultssupporting

confidence: 88%

“…Lower levels of the TCA cycle intermediates are usually replenished, and glutaminolysis is the most important anaplerotic pathway as mentioned above. αKG is used either to generate succinate and ATP/GTP from succinyl-CoA and ADP/GDP (mtSLP) 25 and then pyruvate and lactate through malate 36 (collectively called the oxidative TCA cycle) 28,37 , or to generate citrate for fatty acid synthesis (called reductive carboxylation) 38 , especially in the TCA cycle or OXPHOS-defective cancer cells or cancer cells treated with metformin (a complex I inhibitor) 23,[39][40][41] . Alternatively, glutamine is used to synthesize nucleotides 42 or glutathione 23 .…”

Section: Discussionmentioning

confidence: 99%

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Characterization of metabolic reprogramming by metabolomics in the oncocytic thyroid cancer cell line XTC.UC1

Kurashige

Shimamura

Hamada

et al. 2023

Sci Rep

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Oncocytic thyroid cancer is characterized by the aberrant accumulation of abnormal mitochondria in the cytoplasm and a defect in oxidative phosphorylation. We performed metabolomics analysis to compare metabolic reprogramming among the oncocytic and non-oncocytic thyroid cancer cell lines XTC.UC1 and TPC1, respectively, and a normal thyroid cell line Nthy-ori 3-1. We found that although XTC.UC1 cells exhibit higher glucose uptake than TPC1 cells, the glycolytic intermediates are not only utilized to generate end-products of glycolysis, but also diverted to branching pathways such as lipid metabolism and the serine synthesis pathway. Glutamine is preferentially used to produce glutathione to reduce oxidative stress in XTC.UC1 cells, rather than to generate α-ketoglutarate for anaplerotic flux into the TCA cycle. Thus, growth, survival and redox homeostasis of XTC.UC1 cells rely more on both glucose and glutamine than do TPC1 cells. Furthermore, XTC.UC1 cells contained higher amounts of intracellular amino acids which is due to higher expression of the amino acid transporter ASCT2 and enhanced autophagy, thus providing the building blocks for macromolecules and energy production. These metabolic alterations are required for oncocytic cancer cells to compensate their defective mitochondrial function and to alleviate excess oxidative stress.

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Section: Resultssupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Characterization of metabolic reprogramming by metabolomics in the oncocytic thyroid cancer cell line XTC.UC1

Kurashige

Shimamura

Hamada

et al. 2023

Sci Rep

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“…The underlying basis of chromosomal loss remains unclear, although several hypotheses have been proposed ( 48 , 49 ). Specific chromosomes appear to undergo gains or losses more frequently than others, suggesting that unique selective pressures are exerted on individual chromosomes.…”

Section: Chromosome Gains and Losses In Hccmentioning

confidence: 99%

Genetics, Diagnosis, and Management of Hürthle Cell Thyroid Neoplasms

McFadden

Sadow

2021

Front. Endocrinol.

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Hürthle cell lesions have been a diagnostic conundrum in pathology since they were first recognized over a century ago. Controversy as to the name of the cell, the origin of the cell, and even which cells in particular may be designated as such still challenge pathologists and confound those treating patients with a diagnosis of “Hürthle cell” anything within the diagnosis, especially if that anything is a sizable mass lesion. The diagnosis of Hürthle cell adenoma (HCA) or Hürthle cell carcinoma (HCC) has typically relied on a judgement call by pathologists as to the presence or absence of capsular and/or vascular invasion of the adjacent thyroid parenchyma, easy to note in widely invasive disease and a somewhat subjective diagnosis for minimally invasive or borderline invasive disease. Diagnostic specificity, which has incorporated a sharp increase in molecular genetic studies of thyroid tumor subtypes and the integration of molecular testing into preoperative management protocols, continues to be challenged by Hürthle cell neoplasia. Here, we provide the improving yet still murky state of what is known about Hürthle cell tumor genetics, clinical management, and based upon what we are learning about the genetics of other thyroid tumors, how to manage expectations, by pathologists, clinicians, and patients, for more actionable, precise classifications of Hürthle cell tumors of the thyroid.

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“…ROS act as deleterious molecules that induce cellular damage in several (intra)cellular components and can act as secondary messengers. It was recently demonstrated that metabolic readjustments, and (in)balances of ROS intracellular levels, are related with genomic instability in oncocytic tumors ( 53 ). The aforementioned observations are relevant for the development of the oncocytic phenotype that were studied in the somatic context.…”

Section: Chromosomal Loss and Gains In Oncocytic Tumorsmentioning

confidence: 99%

Inherited Thyroid Tumors With Oncocytic Change

et al. 2021

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Familial non-medullary thyroid carcinoma (FNMTC) corresponds to 5-10% of all follicular cell-derived carcinoma (FCDTC). Oncocytic thyroid tumors have an increased incidence in the familial context in comparison with sporadic FCDTC, encompassing benign and malignant tumors in the same family presenting with some extent of cell oxyphilia. This has triggered the interest of our and other groups to clarify the oncocytic change, looking for genetic markers that could explain the emergence of this phenotype in thyroid benign and malignant lesions, focusing on familial aggregation. Despite some advances regarding the identification of the gene associated with retinoic and interferon-induced mortality 19 (GRIM-19), as one of the key candidate genes affected in the “Tumor with Cell Oxyphilia” (TCO) locus, most of the mutations follow a pattern of “private mutations”, almost exclusive to one family. Moreover, no causative genetic alterations were identified so far in most families. The incomplete penetrance of the disease, the diverse benign and malignant phenotypes in the affected familial members and the variable syndromic associations create an additional layer of complexity for studying the genetic alterations in oncocytic tumors. In the present review, we summarized the available evidence supporting genomic-based mechanisms for the oncocytic change, particularly in the context of FNMTC. We have also addressed the challenges and gaps in the aforementioned mechanisms, as well as molecular clues that can explain, at least partially, the phenotype of oncocytic tumors and the respective clinico-pathological behavior. Finally, we pointed to areas of further investigation in the field of oncocytic (F)NMTC with translational potential in terms of therapy.

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Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma

Cited by 12 publications

References 72 publications

Characterization of metabolic reprogramming by metabolomics in the oncocytic thyroid cancer cell line XTC.UC1

Characterization of metabolic reprogramming by metabolomics in the oncocytic thyroid cancer cell line XTC.UC1

Genetics, Diagnosis, and Management of Hürthle Cell Thyroid Neoplasms

Inherited Thyroid Tumors With Oncocytic Change

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