Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression?
Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression?
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DOI：
10.1007/s00018-012-1186-z
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发表时间：
2013-08
影响因子：
8
通讯作者：
Huettelmaier, Stefan
中科院分区：
文献类型：
--
作者：
Bell, Jessica L.;Waechter, Kristin;Muehleck, Britta;Pazaitis, Nikolaos;Koehn, Marcel;Lederer, Marcell;Huettelmaier, Stefan
胰岛素样生长因子-2 mRNA结合蛋白1、2和3（IGF 2BP 1、IGF 2BP 2、IGF 2BP 3）属于保守的RNA结合癌胚蛋白家族。一些研究表明，这些蛋白质在细胞功能的各个重要方面起作用，例如细胞极化、迁移、形态、代谢、增殖和分化。在这篇综述中，我们讨论了IGF 2BP家族在癌症生物学中的作用，以及这与胚胎发育过程中的拟议功能之间的关系。IGF 2BP主要在胚胎中表达，与成人组织中相对较低或可协商的水平相反。已经发现IGF 2BP 1和IGF 2BP 3在几种侵袭性癌症类型中重新表达。IGF 2BP表达的控制还不清楚;然而，let-7 microRNA、β-catenin（CTNNB 1）和MYC已被提出参与其调节。与许多其他RNA结合蛋白相反，IGF 2BP几乎仅在细胞质中观察到，在细胞质中它们与细胞质核糖核蛋白复合物（mRNP）中的靶mRNA结合。在发育过程中，IGF 2BP是神经细胞迁移和形态发育所必需的，可能分别涉及细胞骨架重塑和动力学的控制。同样，IGF 2BP调节肿瘤衍生细胞中的细胞极化、粘附和迁移。此外，它们与癌症转移和致癌因子（KRAS、MYC和MDR 1）的表达高度相关。然而，由于缺乏“经典的”体内研究，IGF 2BP的促转移作用仍存在争议。尽管如此，IGF 2BP可以提供有价值的癌症治疗靶点，其许多体内作用有待充分阐明。本文的在线版本（doi：10.1007/s 00018 -012-1186-z）包含补充材料，可供授权用户使用。
The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, IGF2BP3) belong to a conserved family of RNA-binding, oncofetal proteins. Several studies have shown that these proteins act in various important aspects of cell function, such as cell polarization, migration, morphology, metabolism, proliferation and differentiation. In this review, we discuss the IGF2BP family’s role in cancer biology and how this correlates with their proposed functions during embryogenesis. IGF2BPs are mainly expressed in the embryo, in contrast with comparatively lower or negotiable levels in adult tissues. IGF2BP1 and IGF2BP3 have been found to be re-expressed in several aggressive cancer types. Control of IGF2BPs’ expression is not well understood; however, let-7 microRNAs, β-catenin (CTNNB1) and MYC have been proposed to be involved in their regulation. In contrast to many other RNA-binding proteins, IGF2BPs are almost exclusively observed in the cytoplasm where they associate with target mRNAs in cytoplasmic ribonucleoprotein complexes (mRNPs). During development, IGF2BPs are required for proper nerve cell migration and morphological development, presumably involving the control of cytoskeletal remodeling and dynamics, respectively. Likewise, IGF2BPs modulate cell polarization, adhesion and migration in tumor-derived cells. Moreover, they are highly associated with cancer metastasis and the expression of oncogenic factors (KRAS, MYC and MDR1). However, a pro-metastatic role of IGF2BPs remains controversial due to the lack of ‘classical’ in vivo studies. Nonetheless, IGF2BPs could provide valuable targets in cancer treatment with many of their in vivo roles to be fully elucidated. The online version of this article (doi:10.1007/s00018-012-1186-z) contains supplementary material, which is available to authorized users.
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