Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression

Anelli, Viviana; Villefranc, Jacques A.; Chhangawala, Sagar; Martinez-McFaline, Raúl; Riva, Eleonora; Nguyen, Anvy; Verma, Akanksha; Bareja, Rohan; Chen, Zhengming; Scognamiglio, Theresa; Elemento, Olivier; Houvras, Yariv

doi:10.7554/elife.20728

Cited by 50 publications

(47 citation statements)

References 38 publications

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“…In a zebrafish model model, BRAF V600E -induced PTC led to EMT activation and thyroid-gland disorganization via the TF TWIST2 (45). Moreover, BRAF V600E activation in the thyroid gland of transgenic mice (Tg-Braf) generated PTC with regions of poorly differentiated thyroid cancer at the late stage (5 months) (46).…”

Section: Tgfβ and Mirnas In Emt Regulationmentioning

confidence: 99%

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

Fuziwara

Saito

Kimura

2019

Archives of Endocrinology and Metabolism

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Thyroid cancer has been rapidly increasing in prevalence among humans in last 2 decades and is the most prevalent endocrine malignancy. Overall, thyroid-cancer patients have good rates of long-term survival, but a small percentage present poor outcome. Thyroid cancer aggressiveness is essentially related with thyroid follicular cell loss of differentiation and metastasis. The discovery of oncogenes that drive thyroid cancer (such as RET, RAS, and BRAF), and are aligned in the MAPK/ERK pathway has led to a new perspective of thyroid oncogenesis. The uncovering of additional oncogenemodulated signaling pathways revealed an intricate and active signaling cross-talk. Among these, microRNAs, which are a class of small, noncoding RNAs, expanded this cross-talk by modulating several components of the oncogenic network-thus establishing a new layer of regulation. In this context, TGFβ signaling plays an important role in cancer as a dual factor: it can exert an antimitogenic effect in normal thyroid follicular cells, and promote epithelial-to-mesenchymal transition (EMT), cell migration, and invasion in cancer cells. In this review, we explore how microRNAs influence the loss of thyroid differentiation and the increase in aggressiveness of thyroid cancers by regulating the dual function of TGFβ. This review provides directions for future research to encourage the development of new strategies and molecular approaches that can improve the treatment of aggressive thyroid cancer.

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Section: Tgfβ and Mirnas In Emt Regulationmentioning

confidence: 99%

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

Fuziwara

Saito

Kimura

2019

Archives of Endocrinology and Metabolism

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“…In future, it would be of interest to extend the atlas by increasing cell numbers and by including single-cell transcriptomics from embryonic and old fish, providing a comprehensive resource for development, homeostasis and aging of the thyroid gland. It would be of further interest to profile zebrafish models of thyroid disorder (42, 43) to understand the cellular and molecular changes underlying organ dysfunction. Combined with the power of CRISPR/Cas9 based screen that we have established for the thyroid gland (27), this resource will provide a roadmap for the functional elucidation of cell type specific programs during thyroid gland growth and homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis reveals cell-cell communication and thyrocyte diversity in the zebrafish thyroid gland

Gillotay

Shankar

Eski

et al. 2020

Preprint

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Single-cell transcriptome analysis reveals cell-cell communication and thyrocyte 1diversity in the zebrafish thyroid gland. 2 Abstract 16The thyroid gland regulates growth and metabolism via production of thyroid hormone in 17 follicles composed of thyrocytes. So far, thyrocytes have been assumed to be a 18 homogenous population. To uncover genetic heterogeneity in the thyrocyte population, 19 and molecularly characterize the non-thyrocyte cells surrounding the follicle, we 20 developed a single-cell transcriptome atlas of the zebrafish thyroid gland. The 6249-cell 21 atlas includes profiles of thyrocytes, blood vessels, lymphatic vessels, immune cells and 22 fibroblasts. Further, the thyrocytes could be split into two sub-populations with unique 23 transcriptional signature, including differential expression of the transcription factor 24 pax2a. To validate thyrocyte heterogeneity, we generated a CRISPR/Cas9-based 25 pax2a knock-in line, which demonstrated specific pax2a expression in the thyrocytes. 26However, a population of pax2a-low mature thyrocytes interspersed within individual 27 follicles could be distinguished, corroborating heterogeneity within the thyrocyte 28 population. Our results identify and validate transcriptional differences within the 29 nominally homogenous thyrocyte population. 30

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“…The first transgenic model of zebrafish PTC has been recently generated in Houvras’ lab [ 57 ] by co-expressing the human oncogene BRAF V600E and the fluorescent protein Td-Tomato in thyrocytes through a thyroid specific promoter, thyroglobulin. This model presented an embryonic phenotype characterized by developmental defects of thyroid structure and absence of hormone T4 production, allowing the study of initial events of transformation.…”

Section: Studying Endocrine Tumors Using Zebrafishmentioning

confidence: 99%

“…Another important observation that came out from this study was that thyroid tumors in adult zebrafish harbor a gene expression signature that stratifies disease recurrence in patients with PTC, identifying patients with significant lower risk of relapse. Besides having clinical significance, these results demonstrated a high similarity between human and zebrafish thyroid cancer [ 57 ].…”

Section: Studying Endocrine Tumors Using Zebrafishmentioning

confidence: 99%

Zebrafish in Translational Cancer Research: Insight into Leukemia, Melanoma, Glioma and Endocrine Tumor Biology

Idilli

Precazzini

Mione

et al. 2017

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Over the past 15 years, zebrafish have emerged as a powerful tool for studying human cancers. Transgenic techniques have been employed to model different types of tumors, including leukemia, melanoma, glioblastoma and endocrine tumors. These models present histopathological and molecular conservation with their human cancer counterparts and have been fundamental for understanding mechanisms of tumor initiation and progression. Moreover, xenotransplantation of human cancer cells in embryos or adult zebrafish offers the advantage of studying the behavior of human cancer cells in a live organism. Chemical-genetic screens using zebrafish embryos have uncovered novel druggable pathways and new therapeutic strategies, some of which are now tested in clinical trials. In this review, we will report on recent advances in using zebrafish as a model in cancer studies—with specific focus on four cancer types—where zebrafish has contributed to novel discoveries or approaches to novel therapies.

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Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression

Cited by 50 publications

References 38 publications

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

Single-cell transcriptome analysis reveals cell-cell communication and thyrocyte diversity in the zebrafish thyroid gland

Zebrafish in Translational Cancer Research: Insight into Leukemia, Melanoma, Glioma and Endocrine Tumor Biology

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