Thyroid C-Cell Biology and Oncogenic Transformation.

Q3 Medicine
Rozita Bagheri-Yarmand, Elizabeth G Grubbs, Marie-Claude Hofmann
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引用次数: 0

Abstract

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. More recently, the integration of multiple biological layers of omics studies has uncovered new pathways of oncogenesis. 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.

甲状腺c细胞生物学和癌性转化。
甲状腺滤泡旁细胞,或通常称为“c细胞”,在血清钙稳态中起作用。血清钙升高触发c细胞释放降钙素,降钙素反过来抑制肠对钙的吸收、破骨细胞对骨的吸收和肾小管细胞对钙的再吸收。甲状腺c细胞的癌性转化被认为是在恶性肿瘤之前通过增生性过程进行的,血清降钙素水平升高是肿瘤负荷的生物标志物。2型多发性内分泌瘤是由RET基因突变激活引起的,这一发现突出了RET- ras - mapk信号通路在甲状腺髓样癌的发生和发展中的作用。已知甲状腺c细胞相对于大多数细胞类型高水平表达RET,因此该受体的异常激活主要针对c细胞,提供了组织特异性肿瘤发生的一个可能原因。RET信号在正常c细胞功能中的作用尚不清楚,尽管降钙素基因转录似乎对RET激活很敏感。除了RET之外,动物肿瘤发生的建模和人类肿瘤候选基因突变的筛选已经发现RAS家族成员的突变和RB1调节途径的失活是c细胞转化的潜在介质。最近,组学研究的多个生物学层面的整合发现了肿瘤发生的新途径。对RET如何在正常c细胞功能和致癌转化过程中与这些途径相互作用的了解越来越多,将有助于开发新的分子靶向治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.60
自引率
0.00%
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