Cancer Stem Cells in the Thyroid

Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

doi:10.3389/fendo.2016.00020

Cited by 43 publications

(32 citation statements)

References 50 publications

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“…In recent years, the cancer stem cell (CSC) theory has emerged as an attractive model to explain many aspects of carcinogenesis including metastasis, recurrence, and therapy resistance (3,4). CSCs are a small subpopulation in the cancer tissue and either self-renew or give rise to non-CSCs to produce heterogeneous tumors.…”

Section: Introductionmentioning

confidence: 99%

JAK/STAT3 and NF-κB Signaling Pathways Regulate Cancer Stem-Cell Properties in Anaplastic Thyroid Cancer Cells

Shiraiwa

Matsuse

Nakazawa

et al. 2019

Thyroid

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Background: Anaplastic thyroid carcinoma (ATC) is still one of the most aggressive and refractory cancers, and a therapy with a new concept needs to be developed. Recently, the research of cancer stem cells (CSCs) has been progressed, and CSCs have been suggested to be responsible for metastasis, recurrence, and therapy resistance. In ATC-CSCs, aldehyde dehydrogenase (ALDH) activity is the most reliable marker to enrich the CSCs; however, it itself is just a marker and is not involved in CSC properties. In the present study, therefore, we aimed to identify key signaling pathways specific for ATC-CSCs. Methods: The siRNA library targeting 719 kinases was used in sphere formation assay and cell survival assay using ATC cell lines to select target molecules specific for the CSC properties. The functions of the selected candidates were confirmed by sphere formation, cell survival, soft-agar, and nude mice xenograft assays using small compound inhibitors. Results: We focused on PDGFR, JAK, and PIM, whose siRNAs had the higher inhibitory effect on sphere formation and also lower/no effect on regular cell growth in both FRO and KTC3 cells. Next, we used inhibitors of PDGFR, JAK, STAT3, PIM and NF-κB, and all of them successfully suppressed sphere formation in a dose-dependent manner but not regular cell growth, conforming the screening results. Inhibition of the JAK/STAT3 and NF-κB pathways also reduced anchorage-independent growth in soft agar and tumor growth in nude mice. Conclusions: These results suggest that JAK/STAT3 and NF-κB signals play important roles in ATC-CSCs. Targeting these signaling pathways may be a promising approach to treat ATC.

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Section: Introductionmentioning

confidence: 99%

JAK/STAT3 and NF-κB Signaling Pathways Regulate Cancer Stem-Cell Properties in Anaplastic Thyroid Cancer Cells

Shiraiwa

Matsuse

Nakazawa

et al. 2019

Thyroid

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“…In agreement with RT-PCR data, we observed a marked increase in the fraction of ALDH positive cells in SDHD depleted NthyOri 3.1 cells (Figure 5B). Unlike NthyOri 3.1 cells, FTC133 cells showed no ALDH activity nor increased “stem” gene expression as these cells are known to lack ALDH activity (Nagayama, et al 2016). …”

Section: Resultsmentioning

confidence: 99%

Sdhd ablation promotes thyroid tumorigenesis by inducing a stem-like phenotype

Ashtekar

Huk

Magner

et al. 2017

Endocrine-Related Cancer

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Mutations in genes encoding enzymes in the tricarboxylic acid cycle (TCA, also known as the Krebs cycle) have been implicated as causative genetic lesions in a number of human cancers, including renal cell cancers, glioblastomas, and pheochromocytomas. In recent studies, missense mutations in the Succinate dehydrogenase (SDH) complex have also been proposed to cause differentiated thyroid cancer. In order to gain mechanistic insight into this process, we generated mice lacking the SDH subunit D (SDHD) in the thyroid. We report that these mice develop enlarged thyroid glands with follicle hypercellularity and increased proliferation. In vitro, human thyroid cell lines with knockdown of SDHD exhibit an enhanced migratory capability, despite no change in proliferative capacity. Interestingly, these cells acquire stem-like features which are also observed in the mouse tumors. The stem-like characteristics are reversed by α-ketoglutarate, suggesting that SDH-associated tumorigenesis results from dedifferentiation driven by an imbalance in cellular metabolites of the TCA cycle. The results of this study reveal a metabolic vulnerability for potential future treatment of SDH-associated neoplasia.

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“…GMI is able to ablate cancer stemness in oral cancer stem cells via inactivating IL‐6/Stat3 (Wang et al, ). Tumor sphere formation has been used to confirm the presence of thyroid CSCs in thyroid cancer cell lines (Nagayama, Shimamura, & Mitsutake, ). Serum‐free medium (SFM) culture in vitro has been used to enrich lung CSCs (Zhu et al, ).…”

Section: Discussionmentioning

confidence: 99%

LncRNA DGCR5 contributes to CSC‐like properties via modulating miR‐330‐5p/CD44 in NSCLC

Ren

Dong

Zeng

et al. 2018

Journal Cellular Physiology

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Non-coding RNAs can exert significant roles various cancers, including NSCLC. Previously, we indicated that lncRNA DGCR5 can promote lung cancer progression through inhibiting hsa-mir-22-3p. In our current study, we investigated the role of DGCR5 in cancer stem cell-like properties of NSCLC. CSCs have been recognized as the frequent cause of tumor metastasis, tumor recurrence, and chemotherapy resistance. Here, lung cancer stem cells were successfully enriched from the parental NSCLC A549, H460, and H1299 cells by using tumor sphere formation assays and side population (SP) assays. We observed that DGCR5 was up-regulated in the enriched CSCs of NSCLC. DGCR5 can inhibit the stemness of NSLCL while overexpression of DGCR5 promoted CSC-like traits. In addition, miR-330-5p was predicted as target of DGCR5 and the correlation between them was validated by dual-luciferase reporter assay, RIP assay, and RNA pull-down assay. Meanwhile, it was found that miR-330-5p was decreased in CSCs of NSCLC. miR-330-5p mimics repressed the stemness while miR-330-5p inhibition enhanced CSC-like properties by targeting CD44. Taken these together, DGCR5 can act as a crucial regulator of CSCs in NSCLC by modulating miR-330-5p/CD44 axis.

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Cancer Stem Cells in the Thyroid

Cited by 43 publications

References 50 publications

JAK/STAT3 and NF-κB Signaling Pathways Regulate Cancer Stem-Cell Properties in Anaplastic Thyroid Cancer Cells

JAK/STAT3 and NF-κB Signaling Pathways Regulate Cancer Stem-Cell Properties in Anaplastic Thyroid Cancer Cells

Sdhd ablation promotes thyroid tumorigenesis by inducing a stem-like phenotype

LncRNA DGCR5 contributes to CSC‐like properties via modulating miR‐330‐5p/CD44 in NSCLC

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