Congenital IGF-1 deficiency protects from cancer: lessons from Laron syndrome.

IF 4.1 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrine-related cancer Pub Date : 2023-09-01 DOI:10.1530/ERC-22-0394
Zvi Laron, Haim Werner
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引用次数: 1

Abstract

Many clinical and experimental studies have implicated the growth hormone (GH)-insulin-like growth factor (IGF-1) axis with the progression of cancer. The epidemiological finding that patients with Laron syndrome (LS), the best-characterized disease under the spectrum of congenital IGF-1 deficiencies, do not develop cancer is of major scientific and translational relevance. The evasion of LS patients from cancer emphasizes the central role of the GH-IGF-1 system in cancer biology. To identify genes that are differentially expressed in LS and that might provide a biological foundation for cancer protection, we have recently conducted genome-wide profiling of LS patients and normal controls. Analyses were performed on immortalized lymphoblastoid cell lines derived from individual patients. Bioinformatic analyses identified a series of genes that are either over- or under-represented in LS. Differential expression was demonstrated in a number of gene families, including cell cycle, metabolic control, cytokine-cytokine receptor interaction, Jak-STAT and PI3K-AKT signaling, etc. Major differences between LS and controls were also noticed in pathways associated with cell cycle distribution, apoptosis, and autophagy. The identification of novel downstream targets of the GH-IGF-1 network highlights the biological complexity of this hormonal system and sheds light on previously unrecognized mechanistic aspects associated with GH-IGF-1 action in the cancer cell.

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先天性IGF-1缺乏可以预防癌症:从Laron综合征的经验教训。
许多临床和实验研究表明,生长激素(GH)-胰岛素样生长因子(IGF-1)轴与癌症的进展有关。Laron综合征(LS)是先天性IGF-1缺乏症谱系中最具特征的疾病,其患者不发展为癌症,这一流行病学发现具有重大的科学和转化意义。LS患者对癌症的逃避强调了GH-IGF-1系统在癌症生物学中的核心作用。为了确定LS中差异表达的基因,并可能为癌症保护提供生物学基础,我们最近对LS患者和正常对照进行了全基因组分析。对来自个体患者的永生化淋巴母细胞样细胞系进行了分析。生物信息学分析确定了一系列在LS中表现过度或不足的基因。在细胞周期、代谢控制、细胞因子-细胞因子受体相互作用、Jak-STAT和PI3K-AKT信号传导等多个基因家族中均存在差异表达。LS与对照组在细胞周期分布、凋亡和自噬相关的通路上也存在主要差异。GH-IGF-1网络的新下游靶点的鉴定突出了这一激素系统的生物学复杂性,并揭示了以前未被认识的与GH-IGF-1在癌细胞中的作用相关的机制方面。
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来源期刊
Endocrine-related cancer
Endocrine-related cancer 医学-内分泌学与代谢
CiteScore
7.80
自引率
2.60%
发文量
138
审稿时长
6-12 weeks
期刊介绍: Endocrine-Related Cancer is an official flagship journal of the Society for Endocrinology and is endorsed by the European Society of Endocrinology, the United Kingdom and Ireland Neuroendocrine Society, and the Japanese Hormones and Cancer Society. Endocrine-Related Cancer provides a unique international forum for the publication of high quality original articles describing novel, cutting edge basic laboratory, translational and clinical investigations of human health and disease focusing on endocrine neoplasias and hormone-dependent cancers; and for the publication of authoritative review articles in these topics. Endocrine neoplasias include adrenal cortex, breast, multiple endocrine neoplasia, neuroendocrine tumours, ovary, prostate, paraganglioma, parathyroid, pheochromocytoma pituitary, testes, thyroid and hormone-dependent cancers. Neoplasias affecting metabolism and energy production such as bladder, bone, kidney, lung, and head and neck, are also considered.
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