Thyroid cancer stem-like cells and epithelial-mesenchymal transition in thyroid cancers

Hardin, Heather; Montemayor‐Garcia, Celina; Lloyd, Ricardo V.

doi:10.1016/j.humpath.2013.01.009

Cited by 30 publications

(23 citation statements)

References 57 publications

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“…11,12 Evidence in favour of this multistep carcinogenesis model includes, the presence of well-differentiated TC within ATC specimens and the coexistence of BRAF gene and TP53 gene mutations in both undifferentiated and differentiated carcinomas. 13,14 However, this model is not in accordance with the rare occurrence of RET/PTC and PAX8/PPARG rearrangements in ATC 15 and the low turnover rate of thyroid follicular cells (about five renewals per lifetime) that reduces the possibility of accumulating the mutations needed for transformation. 8,[16][17][18] The existence of several differentiation degrees has led to the assumption that TC cells are derived from remnants of fetal thyroid cells, such as stem cells (SCs) or precursors, rather than mature follicular cells.…”

Section: Introductionmentioning

confidence: 87%

Normal vs cancer thyroid stem cells: the road to transformation

et al. 2015

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Recent investigations in thyroid carcinogenesis have led to the isolation and characterisation of a subpopulation of stem-like cells, responsible for tumour initiation, progression and metastasis. Nevertheless, the cellular origin of thyroid cancer stem cells (SCs) remains unknown and it is still necessary to define the process and the target population that sustain malignant transformation of tissue-resident SCs or the reprogramming of a more differentiated cell. Here, we will critically discuss new insights into thyroid SCs as a potential source of cancer formation in light of the available information on the oncogenic role of genetic modifications that occur during thyroid cancer development. Understanding the fine mechanisms that regulate tumour transformation may provide new ground for clinical intervention in terms of prevention, diagnosis and therapy.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.138

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Section: Introductionmentioning

confidence: 87%

Normal vs cancer thyroid stem cells: the road to transformation

et al. 2015

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“…EMT is a mechanism that generates further CSCs with increased invasiveness and a metastatic phenotype (61). In addition, EMT exerts a critical function in tumor recurrence, and is associated with a loss of E-cadherin expression by genes that repress E-cadherin, including Snail, Slug, zinc-finger E-box-binding (ZEB)1, ZEB2 and Twist1 (62). During EMT, cells become less adherent, lose polarity and acquire an invasive phenotype (63).…”

Section: Thyroid Cscsmentioning

confidence: 99%

Cancer stem cells as a potential therapeutic target in thyroid carcinoma

Vicari¹,

Colarossi²,

Giuffrida³

et al. 2016

Oncology Letters

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Abstract.A number of studies have indicated that tumor growth and proliferation is dependent on a small subset of cells, defined as cancer stem cells (CSCs). CSCs have the capability to self-renew, and are involved with cancer propagation, relapse and metastatic dissemination. CSCs have been isolated from numerous tissues, including normal and cancerous thyroid tissue. A regulatory network of signaling pathways and microRNAs (miRNAs) control the properties of CSCs. Differentiated thyroid carcinoma is the most common type of endocrine cancer, with an increasing incidence. Anaplastic thyroid carcinoma is the most rare type of endocrine cancer; however, it also exhibits the highest mortality rate among thyroid malignancies, with an extremely short survival time. Thyroid CSCs are invasive and highly resistant to conventional therapies, including radiotherapy and chemotherapy, which results in disease relapse even when the primary lesion has been eradicated. Therefore, targeting thyroid CSCs may represent an effective treatment strategy against aggressive neoplasms, including recurrent and radioresistant tumors. The present review summarizes the current literature regarding thyroid CSCs and discusses therapeutic strategies that target these cells, with a focus on the function of self-renewal pathways and miRNAs. Elucidation of the mechanisms that regulate CSC growth and survival may improve novel therapeutic approaches for treatment-resistant thyroid cancers.

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“…In fact, somatic RET M918T mutation in male germ cells is associated with enhanced stem cell proliferation and provides a plausible mechanism for the paternal origin of MEN2B [216]. While it remains to be formally examined, germline mutation of RET is also predicted to increase the neural crest progenitor cell population, thereby providing a larger pool of tumor initiating or the so call “cancer stem cells.” A thyroid cancer stem cell model has been proposed for both medullary and nonmedullary thyroid cancer [217–219]. Support for a role in MTC derives from the observations that C-cells or their progenitors play a role in adult thyroid regeneration [220], and that RET mutation is associated with EGF/FGF independent [221], as well as, 5-fluorouracil resistant MTC tumorsphere growth [222].…”

Section: Considering Mechanisms Of C-cell Tumor Initiation and Promentioning

confidence: 99%

Thyroid C-Cell Biology and Oncogenic Transformation

Cote

Grubbs

Hofmann

2015

Medullary Thyroid Carcinoma

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The thyroid parafollicular cell, or commonly named “C-cell,” functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that Multiple Endocrine Neoplasia, type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma. Thyroid C-cells are known to express RET at high levels relative to most cell types, therefore aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations has uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation will help in the development of novel molecular targeted therapies.

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Thyroid cancer stem-like cells and epithelial-mesenchymal transition in thyroid cancers

Cited by 30 publications

References 57 publications

Normal vs cancer thyroid stem cells: the road to transformation

Normal vs cancer thyroid stem cells: the road to transformation

Cancer stem cells as a potential therapeutic target in thyroid carcinoma

Thyroid C-Cell Biology and Oncogenic Transformation

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