Linking loss of sodium-iodide symporter expression to DNA damage

Lyckesvärd, Madeleine Nordén; Kapoor, Nirmal; Ingeson-Carlsson, Camilla; Carlsson, Therese; Karlsson, Jens; Postgård, Per; Himmelman, Jakob; Forssell-Aronsson, Eva; Hammarsten, Ola; Nilsson, Mikael

doi:10.1016/j.yexcr.2016.04.015

Cited by 8 publications

(3 citation statements)

References 58 publications

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“…MYC-stimulated cell proliferation may potentiate genotoxic stress induced by oncogenic drivers. NIS repression can also result from DNA damage involving ATM-mediated mechanisms [33]. We noted that dermatopontin is among the top-ranked differentially expressed genes among both the high and low NIS groups.…”

Section: Discussionmentioning

confidence: 73%

Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer

Lee

Kuo

Tsai

et al. 2022

CIMB

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Sodium iodide symporter (NIS) expression in thyroid follicular cells plays an important role in normal physiology and radioactive iodine therapy for thyroid cancer. Loss of NIS expression is often seen in thyroid cancers and may lead to radioiodine refractoriness. To explore novel mechanisms of NIS repression beyond oncogenic drivers, clinical and RNA-seq data from the thyroid cancer dataset of The Cancer Genome Atlas were analyzed. Propensity score matching was used to control for various genetic background factors. We found that tumoral NIS expression was negatively correlated with tumor size. Additionally, low NIS expression was the only factor associated with recurrence-free survival in a Cox multivariate regression analysis. After matching for clinicopathologic profiles and driver mutations, the principal component analysis revealed distinct gene expressions between the high and low NIS groups. Gene set enrichment analysis suggested the downregulation of hedgehog signaling, immune networks, and cell adhesions. Positively enriched pathways included DNA replication, nucleotide excision repair, MYC, and Wnt/β-catenin pathways. In summary, we identified several potential targets which could be exploited to rescue the loss of NIS expression and develop redifferentiation strategies to facilitate radioactive iodine therapy for thyroid cancer.

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Section: Discussionmentioning

confidence: 73%

Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer

Lee

Kuo

Tsai

et al. 2022

CIMB

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“…In the present examination it has been elucidated that NIS protein affected by the BRAF V600E gene in CD133 pos cells. However, the affected BRAF V600E gene on NIS gene/protein expression (Bastos et al, 2015) is one agent of several factors that cause a loss of NIS expression (Lyckesvärd et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Targeting the BRAF Signaling Pathway in CD133pos Cancer Stem Cells of Anaplastic Thyroid Carcinoma

Bozorg-Ghalati

Hedayati

Dianatpour

et al. 2019

Asian Pac J Cancer Prev

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Background:Cancer stem cells (CSCs) with a self-renewal ability in tumor cells population, execute a pivotal function in tumorigenesis, retrogression, and metastasis of malignant cancers such as anaplastic thyroid carcinoma (ATC).Materials and Methods:In this study, we isolated CSCs subpopulation with CD133 surface marker from three ATC cell lines by magnetic cell sorting assay. After confirming the segregation by the flow cytometry method, BRAF and sodium-iodide symporter (NIS) genes were investigated in them before and after incubation with BRAF inhibitor. Also, we evaluated the NIS protein expression and localization.Results:Established upon q-RT PCR data, when compared to human normal thyrocytes, the BRAFV600E gene was over-expressed in CD133pos cells (>1705.99 ± 55.55 fold, Mean ± SEM, n=3, P- value<0.05), whilst the expression of NIS gene was very restricted (< 0.0008 ± 5.43 fold, Mean ± SEM, n=3, P- value<0.05) in them. Also, our results showed that BRAF inhibition affected NIS protein expression and localization.Conclusions:Current study showed that the differentiate genes/proteins expression can be induced in the CSCs via focus on signal transduction pathways and targeting their molecules, that are involved in expression of these genes/proteins. Therefore, attention to targeting CSCs along with routine thyroid cancer therapy, can help to ATC treatment.

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“…For example, 131 I is a radionuclide commonly used in clinical theranostics due to the γ‐ray emission (364 keV) for SPECT imaging and β‐ray emission (606 keV) for RT. To be specific, the β‐ray emission of 131 I can induce the break of DNA strands to lead to cell death . During the past few years, our group has been extensively exploring the synthesis of 131 I‐labeled G5 dendrimers modified with various targeting ligands for SPECT imaging and RT treatment of different types of cancer 19b,26.…”

Section: Radiolabeled Dendrimer‐based Nanodevices For Rt and Theranosmentioning

confidence: 99%

PAMAM Dendrimer‐Based Nanodevices for Nuclear Medicine Applications

Xiao

Shi

et al. 2019

Macromolecular Bioscience

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Nuclear medicine, involving nuclear medicine imaging and radiotherapy (RT), has become a mainstay of theranostics in the field of nanomedicine and several examples have been successfully translated into clinical practice. The combination of radionuclides with dendrimers has long been investigated in nuclear imaging, such as positron emission tomography (PET) and single‐photon emission computed tomography (SPECT), providing functional information for whole body quantitative analysis with high sensitivity due to the unique structural advantages of the dendrimer platform. Besides, radioisotopes with both therapeutic and imaging functionalities can also be combined with dendrimer platforms for theranostic applications. In this review, the recent advances in the development of radionuclide‐labeled poly(amidoamine) dendrimer‐based nanodevices for targeted PET, SPECT, SPECT/computed tomography, SPECT/magnetic resonance imaging of tumors, RT, as well as for SPECT‐imaging‐guided RT of cancer are summarized. Current restrictions hindering the clinical translation of dendrimer‐based nuclear nanodevices and future prospects are also discussed.

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Linking loss of sodium-iodide symporter expression to DNA damage

Cited by 8 publications

References 58 publications

Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer

Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer

Targeting the BRAF Signaling Pathway in CD133pos Cancer Stem Cells of Anaplastic Thyroid Carcinoma

PAMAM Dendrimer‐Based Nanodevices for Nuclear Medicine Applications

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