Hippo通路及YAP基因研究的新进展

Hippo通路是近年来在果蝇体内发现的一条新的细胞信号通路,主要的功能包括调控器官体积、保持细胞增殖凋亡平衡,参与细胞接触性抑制的调节,通路的调控异常导致肿瘤发生。YAP基因是Hippo通路最主要的调控因子。在本文中,我们主要介绍Hippo通路的组成,具体调控机制,YAP基因及其在肿瘤生成中的作用。     

Hippo通路及YAP基因研究的新进展

Hippo通路是近年来在果蝇体内发现的一条新的细胞信号通路,主要的功能包括调控器官体积、保持细胞增殖凋亡平衡,参与细胞接触性抑制的调节,通路的调控异常导致肿瘤发生。YAP基因是Hippo通路最主要的调控因子。在本文中,我们主要介绍Hippo通路的组成,具体调控机制,YAP基因及其在肿瘤生成中的作用。     

Hippo信号通路调控肿瘤耐药的研究进展

Hippo信号通路是调节器官体积大小与平衡细胞增殖凋亡的重要通路。Hippo信号通路可能参与肿瘤化疗耐药,通过对该通路的干预可以提高肿瘤的化疗敏感性,从而逆转化疗耐药。本文将Hippo信号通路调控肿瘤化疗耐药的研究进展作一综述。     

Hippo通路和相关长链非编码RNA（LncRNA）与肿瘤关系的研究进展

Hippo信号通路是近年来在果蝇体内发现的一条新的细胞信号通路,主要功能包括保持细胞增殖凋亡、调控器官体积,其调控异常将导致肿瘤的发生。LncRNA（long non-coding RNA,LncRNA）是一类长度大于200个核苷酸的非编码RNA,缺少特异开放阅读框,不具备蛋白质编码功能。研究显示,LncRNA与肿瘤的发生、发展、转移密切相关。本文就Hippo信号通路和相关LncRNA与肿瘤关系的研究进展做一综述。     

SAV1在肿瘤中作用的研究进展

摘 要：SAV1是哺乳动物Hippo信号通路的核心激酶之一,主要参与调节细胞增殖与器官发育。近期研究发现,在众多肿瘤组织中SAV1均处于低表达或者缺失状态,SAV1敲除的小鼠模型更是能诱导出各种肿瘤的发生,表明SAV1的缺失与肿瘤的发生之间存在着直接或间接的分子机制。全文就近年有关SAV1在不同肿瘤中的研究进展进行系统综述,以期为发现新的肿瘤治疗靶点提供理论依据。     

YAP 与肿瘤干细胞相关性研究进展*

YAP 是一种多功能蛋白,可以与不同的转录因子相互作用激活基因的表达。YAP 作为活化Hippo途径的关键转录调节蛋白在调节器官大小、细胞自我更新、干细胞和组织特异性祖细胞扩增等方面发挥重要作用,在Hippo途径中MST 1/ 2 激酶和其结合蛋白SAV 共同磷酸化激酶LATS1/ 2,激活的LATS1/ 2 磷酸化YAP 从而抑制YAP 蛋白的活性。近年来,大量的研究已经在胚胎干细胞、神经干细胞、造血干细胞中发现YAP 的高表达能够维持干细胞干性并且已经成为维持干性的标志物,随后的研究发现信号通路可能与肿瘤干细胞（CSC）分化密切相关。本文主要讨论YAP 在维持干细胞及肿瘤干细胞干性方面的作用。      

Hippo通路与乳腺癌发生发展的作用研究进展与应用前景

在发病率逐年增高和死亡率居高不下的全球大背景下,乳腺癌一直是科研领域的研究热点。Hippo通路广泛涉及了从乳腺正常发育至乳腺癌发生发展、侵袭转移及耐药等一系列过程。该综述以乳腺癌总人群发病特征及Hippo通路发展历程为背景,围绕肿瘤干细胞、上皮-间质转化及凋亡三方面介绍了Hippo通路对乳腺癌肿瘤表型的调控,最后从临床应用前景上做出展望,介绍了Hippo通路成分对乳腺癌患者的预后作用及可能提供的药物治疗靶点。     

14-3-3ζ对肿瘤相关信号通路调控作用的研究进展

随着分子生物学领域的不断研究发现,在肿瘤的发生过程中,往往伴随着异常信号通路的激活。14-3-3ζ为14-3-3蛋白家族的一个亚型,近年来发现14-3-3ζ可以调控肿瘤相关的多条信号通路以促进肿瘤的进展,按照作用机制分类,主要包括对 NF-κB信号通路、PI3K/AKT信号通路、JAK-STAT信号通路、TGF-β信号通路、Wnt信号通路、Hippo信号通路等的调控。14-3-3ζ可通过调控上述信号通路促进癌细胞增殖和侵袭、诱导细胞凋亡、增加糖酵解、调节肿瘤炎症和免疫等,从而发挥促进肿瘤发生发展的作用。因此,14-3-3ζ影响肿瘤相关信号通路的分子机制对于肿瘤的诊治可能尤为重要。本文将重点介绍有关14-3-3ζ对恶性肿瘤信号通路调控作用的研究进展,以期为肿瘤发病机制的深入研究及靶向药物研发提供新思路和方向。     

Hippo-YAP/TAZ信号通路调控铁死亡对肿瘤影响的研究进展

铁死亡是一种新型的铁依赖的程序性细胞死亡，常伴随脂质过氧化物的异常累积。Hippo 通路是一种高度进化保守的蛋白激酶信号通路，通过调节下游效应蛋白YAP/TAZ的亚细胞定位和蛋白稳定性，参与调节细胞的多种生命活动，包括组织生长、干细胞分化、肿瘤的发生发展等。近年来的研究发现，Hippo-YAP/TAZ信号通路通过细胞密度、细胞接触、细胞代谢、机械信号等多种细胞外途径影响肿瘤细胞对铁死亡的敏感性，在不同类型的肿瘤组织中通过特定的刺激条件、铁死亡靶向蛋白及其分子机制，影响泌尿、生殖、消化、呼吸和内分泌系统等肿瘤的发生和发展。Hippo-YAP/TAZ信号通路作为铁死亡新的调节机制，其激活为转移性及耐药性肿瘤的治疗提供了新的思路和方向。     

Hippo信号通路在肺癌中的研究进展

肺癌是全世界范围内肿瘤相关性死亡的首要原因,每年死亡人数超过100万人,占全球癌症死亡人数的五分之一.虽然目前在手术、放化疗、靶向治疗、免疫治疗肺癌方面取得了一定进展,但患者的预后仍不理想.因此,亟待寻找评价预后的分子标志物和肺癌的治疗新靶点,为肺癌患者提供生存获益的有效方法.近年来,Hippo信号通路逐渐成为国内外肿瘤研究领域中新兴且热门的研究方向.Hippo信号通路激活时,其核心组件MST/MOB、LATS 1/2等能抑制转录的共激活剂YAP/TAZ的转录,二者被磷酸化并滞留在细胞浆中,从而抑制肺癌的发生发展.因此Hippo信号通路在临床应用中的潜在价值也越来越受关注.本篇文章总结了Hippo信号通路核心组成元件及上下游调控因子在肺癌形成进展过程中的重要作用和分子机制,并对Hippo信号通路的研究前景进行展望.     

Hippo信号通路在乳腺癌转移中的作用

Hippo是新发现的一种非常保守的信号传导通路,其主要成分在多种癌症中出现突变和表达失调,促进了恶性肿瘤的发生发展。但有关Hippo信号通路在乳腺癌中的研究较少,分子调控机制尚不完全清楚。现就Hippo信号通路在乳腺癌转移中的作用进行综述,以期明确Hippo信号通路对乳腺癌发生、发展和转移可能起到的作用,为抑制乳腺癌的转移提供新思路。     

Hippo pathway monomerizes STAT3 to regulate prostate cancer growth

Prostate cancer ranks among the most commonly diagnosed malignancies for men and has become a non‐negligible threat for public health. Interplay between inflammatory factors and cancer cells renders inflammatory tissue environment as a predisposing condition for cancer development. The Hippo pathway is a conserved signaling pathway across multiple species during evolution that regulates tissue homeostasis and organ development. Nevertheless, whether Hippo pathway regulates cancer‐related inflammatory factors remains elusive. Here, we show that high cell density–mediated activation of the Hippo pathway blunts STAT3 activity in prostate cancer cells. Hippo pathway component MST2 kinase phosphorylates STAT3 at T622, which is located in the SH2 domain of STAT3. This phosphorylation blocks the SH2 domain in one STAT3 molecule to bind with the phosphorylated Y705 site in another STAT3 molecule, which further counteracts IL6‐induced STAT3 dimerization and activation. Expression of a nonphosphorylatable STAT3 T622A mutant enhances STAT3 activity and IL6 expression at high cell density and promotes tumor growth in a mice xenograft model. Our findings demonstrate that STAT3 is a novel phosphorylation substrate for MST2 and thereby highlight a regulatory cascade underlying the crosstalk between inflammation and the Hippo pathway in prostate cancer cells.     

Capturing the mammalian Hippo: Elucidating its role in cancer

The Hippo pathway is an evolutionarily conserved kinase cascade involved in cell growth, apoptosis, development and migration. It is also crucial for stem cell self‐renewal and the maintenance of genomic stability. In addition, this pathway has the unique capacities to sense aspects of tissue architecture, such as cell polarity and mechanical tensions imposed by the surrounding microenvironment, and to control organ size and shape. All of these properties are frequently altered in tumor cells. In this review, we summarize how dysregulation of mammalian Hippo signaling is implicated in cancer.     

Hippo signaling in oval cells and hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer mortality world wide. Despite continuing development of new therapies, the prognosis for patients with HCC remains extremely poor. In part, this may relate to molecular abnormalities that stimulate HCC tumorigenesis and also contribute to reduced sensitivity to standard treatment. Increasing evidence has revealed the importance of liver cancer stem cells in hepatocarcinogenesis. Although widely investigated, the signaling pathways important for liver cancer stem cells in liver tumor initiation and progression are poorly understood. The Hippo signaling pathway was identified in Drosophila as an essential regulator of cell proliferation and apoptosis. Recently, Hippo pathway has been implicated in multiple events during development and it has also been proposed to play a vital role in several tumor types, especially in hepatocellular carcinoma. Strong evidences also proved the significant role of the Hippo signaling pathway in oval cell activation. As suggested, hippo signaling has a dual regulation of Hippo in liver tumor suppression as well as transition of oval cells to fully differentiated hepatocytes. Delineation of the malfunction of Hippo signaling pathway in HCC may lead to better understanding of hepatocarcinogenesis, rational medical therapy for HCC and possible therapy for other tumors. Here, we provide a historical review of this potent growth-regulatory pathway in HCC and highlight outstanding questions that will likely be the focus of future investigation.