TGF-β/Smads信号传导通路与肿瘤关系研究进展

转化生长因子β(transforming growth factor-β,TGF-β)是以大分子无活性的蛋白前体形式由正常细胞和转化细胞分泌的,需激活后才能发挥其生物学活性。激活的TGF-β与TβRⅡ结合形成二聚体使TSR Ⅰ磷酸化,随后R-Smad亦被磷酸化并诱导其复合物转至细胞核内。TGF-β对许多类型的细胞发挥广泛的生物学作用,对细胞的生长具有双重作用。但这些细胞因受体表达下降或缺失、Smad突变而致的信号传导异常、激活潜态TGF-β能力的丧失及调控TGF-β转录传导的功能性基因丢失而失去对TGF-β的反应性,从而导致肿瘤的发生。同时,TGF-β在G1期发挥它调节细胞周期的作用。     

肿瘤细胞信号传导的研究进展

细胞信号传导紊乱是肿瘤细胞生长的特征，信号传导的高效性及信号通路间的交叉，显示信号传导在肿瘤发生、发展中发挥重要作用，对信号通路的深入了解必将促进肿瘤治疗的革新。     

TGF-β／Smads信号传导通路与肿瘤关系研究进展

转化生长因子β(transforming growth factor-β，TGF-β)是以大分子无活性的蛋白前体形式由正常细胞和转化细胞分泌的，需激活后才能发挥其生物学活性。激活的TGF-β与TβR Ⅱ结合形成二聚体使TβR Ⅰ磷酸化，随后R-Smad亦被磷酸化并诱导其复合物转至细胞核内。TGF-β对许多类型的细胞发挥广泛的生物学作用，对细胞的生长具有双重作用。但这些细胞因受体表达下降或缺失、Smad突变而致的信号传导异常、激活潜态TGF-β能力的丧失及调控TGF-β转录传导的功能性基因丢失而失去对TGF-β的反应性．从而导致肿瘤的发生。同时，TGF-β在G1期发挥它调节细胞周期的作用。     

Hedgehog信号通路在三阴型乳腺癌中的研究进展

乳腺癌是女性常见的恶性肿瘤之一,严重影响妇女身心健康甚至危及生命。三阴型乳腺癌(triple negative breast cancer,TNBC)作为乳腺癌的重要临床亚型之一,由于缺少相应的治疗方法,成为现阶段的研究热点。已有研究表明Hedgehog信号通路在乳腺癌尤其是TNBC中起非常重要的作用。该文针对Hedgehog信号通路在TNBC中的研究进展进行综述。     

Wnt/β-catenin 信号通路在肿瘤干细胞中作用研究进展

 Wnt 信号通路是调控细胞生长、运动和分化的关键途径，在胚胎和器官发育以及维持干细胞的自我更新方面起重要作用。近年来的研究表明^[1]，Wnt/β-连环蛋白（β-catenin）信号通路的不恰当激活，参与了肿瘤的发生及其侵袭转移的过程，而且还与肿瘤干细胞（tumor stem cells，TSC）的关系密切，该通路可能通过作用于TSC而引起肿瘤产生耐受及复发，作用机制与其作用于干细胞的机制类似，从而为肿瘤的治疗提供了新的突破口。本文就 Wnt 通路中最为常见的 Wnt/β-catenin 信号通路在干细胞、肿瘤和 TSC 中作用的研究现状做一简要概述。......     

肿瘤细胞信号传导的研究进展

细胞信号传导紊乱是肿瘤细胞生长的特征,信号传导的高效性及信号通路间的交叉,显示信号传导在肿瘤发生、发展中发挥重要作用,对信号通路的深入了解必将促进肿瘤治疗的革新。     

DLL4／Notch信号传导途径调节肿瘤血管生成的研究进展

Folkman[1]于1971年提出的"肿瘤血管生成依赖学说"使人们对肿瘤生长与新生血管形成的关系有了较为深刻的认识,抗肿瘤新生血管形成成为肿瘤综合治疗的重要策略之一。其中,研究较多、也最有价值的是通过阻断血管内皮生长因子(vascular endothelial growth factor,VEGF)及其主要受体(VEGFR2)来     

MAPK/JNK信号传导通路研究进展

JNK信号途径参与如胚胎发育、免疫反应、细胞分化等许多正常的生理过程。近年来研究表明 ,JNK信号途径也参与许多病理过程 :JNK介导心脏肥大反应 ,与 型糖尿病发病有关 ,介导胰腺 b细胞凋亡 ;JNK信号途径的异常活化与多种人类肿瘤的发生发展密切相关 ,因此 JNK是一个潜在的治疗分子靶 ,已引起人们的关注。对其功能及作用的分子机制的深入研究 ,有助于我们对 JNK相关疾病的了解和寻找可能的干预和治疗途径     

信号传递途径JAK-STAT研究进展

细胞信号传递途径JAK-STAT参与细胞因子在细胞生成、分化,胚胎发育及机体免疫等生物学作用的基因调控的配体与大多数缺少激酶结构域的受体结合后,JAK激酶通过和受体聚合以及JAK的酪氨酸磷酸化激活,使受体和STAT蛋白磷酸化,后者直接参与基因调控。     

JAK/STAT3信号通路调控肿瘤及其相关生物功能的研究进展

JAK/STAT3信号通路是细胞信号通路中重要的信号传导通路之一,通过影响下游多种效应分子的活化状态,对细胞凋亡和增殖起着关键的作用,并且还诱导胚胎发育、肝脏再生、糖酵解和炎性反应、上皮间质转化和血管再生等一系列生物发生过程,与人类肿瘤的发生发展密切相关。     

Protein ISGylation modulates the JAK-STAT signaling pathway

ISG15 is one of the most strongly induced genes upon viral infection, type I interferon (IFN) stimulation, and lipopolysaccharide (LPS) stimulation. Here we report that mice lacking UBP43, a protease that removes ISG15 from ISGylated proteins, are hypersensitive to type I IFN. Most importantly, in UBP43-deficient cells, IFN-beta induces a prolonged Stat1 tyrosine phosphorylation, DNA binding, and IFN-mediated gene activation. Furthermore, restoration of ISG15 conjugation in protein ISGylation-defective K562 cells increases IFN-stimulated promoter activity. These findings identify UBP43 as a novel negative regulator of IFN signaling and suggest the involvement of protein ISGylation in the regulation of the JAK-STAT pathway.     

JAK／STAT信号通路对RA调控作用的研究进展

JAK／STAT信号通路是近年发现的重要的信号转导通路,参与调控人体多种器官和组织的发育、生长和分化。研究证实,在RA起病和关节破坏过程中,JAK／STAT信号通路发挥着重要的调控作用。JAK／STAT信号通路通过多种途径参与炎性反应,与RA关系密切。闪此,了解JAK／STAT信号通路对RA的调控层次关系,能为开发新的抗RA药物提供新的际遇。     

Anticancer effect of salidroside on colon cancer through inhibiting JAK2/STAT3 signaling pathway

Salidroside is considered to have anti-tumor properties. We investigate its effects on colon carcinoma SW1116 cells. Cell viability was assessed by CCK-8. Propidium iodide (PI) staining was used to determine the cell cycle by flow cytometry. The migration and invasion were detected by Transwell. Western blot was used to detect the expression of STAT3 signal related proteins. As the result, high concentrations of salidroside (10, 20. 50 μg/ml) significantly inhibited proliferation of SW1116 cells in a parallelly, cell cycle arrest was increased at the G0/G1 phase after salidroside treatment. Furthermore, salidroside inhibited migration and invasion of SW1116 cells. Salidroside treatment decreased proteins expression of phosphorylation levels in JAK2/STAT3 signaling, while MMP-2 and MMP-9 proteins levels were decreased and protein expression of VEGF and VEGFR-2 were down-regulated. In Conclusion, salidroside inhibited proliferation, decreased the migration and invasion of SW1116 cells in JAK2/STAT3-dependent pathway, the specific mechanisms need further study.     

Runx1 promotes the development of glioma cells by regulating JAK-STAT signalling pathway

IntroductionHuman glioma is known as the most frequent and primary malignant tumour of the central nervous system with high aggression and poor prognosis. Runx1 is essential for haematopoiesis and is associated with tumour progression in several types of cancers. Therefore, this study aimed to investigate the effect and the possible regulatory mechanisms of Runx1 in glioma.Material and methodsThe expression of Runx1 in human glioma tissues was determined by qRT-PCR and immunohistochemistry (IHC). Subsequently, the effect of Runx1 on the glioma cell viability, migration, invasion and the protein level of p21, cyclin D1, MMP2, and MMP4 were detected by MTT, wound healing, transwell assays, and western blot, respectively, in U-138MG and U-251MG cell lines. We then explored the role of Runx1 in vivo by establishing a tumour-bearing mouse model.ResultsThe expression of Runx1 was significantly up-regulated in human glioma tissues and closely associated with tumour grade. Glioma patients with high Runx1 expression had decreased survival rate compared to those with low Runx1 level. Runx1 knockdown inhibited glioma cell viability, migration, invasion, and clone formation, while STAT3 suppressed these inhibitions. Moreover, Runx1 inhibited the activation of SOCS3/SOCS4 promoter, which in turn activated JAK/STAT3 signalling pathway. The tumour volume and weight of the siRunx1 group were lower than in the control group and the tumour mass grow more slowly as well.ConclusionsRunx1 promotes the development of glioma cells via JAK/STAT signalling pathway by inhibiting the activation of SOCS3/SOCS4 promoter.     

Wnt信号通路与非小细胞肺癌的研究进展

Wnt信号通路在人类恶性肿瘤有着重要的调控作用。在非小细胞肺癌(NSCLC)细胞系,抑制Wnt通路能降低肿瘤扩散。Wnt信号因子影响非小细胞肺癌细胞的生长、分化、疾病的预后及化疗抗药性,可作为晚期非小细胞肺癌靶向治疗的新选择。     

Trichosanthin inhibits the proliferation of cervical cancer cells and downregulates STAT-5/C-myc signaling pathway

Background

Previous studies have indicated that Trichosanthin (TCS) exerts anti-virus, immunoregulation and a broad spectrum anti-tumor pharmacological activities. Trichosanthin is a promising agent for the treatment of cervical cancer. However, the exact effects and potential mechanism of TCS on cervical cancer are not well known.

Wnt信号通路与神经管缺陷关系的研究进展

神经管缺陷(neural tube,defects,NTD)是神经管闭合不全引起的一类先天性畸形,主要包括无脑、脑膨出、脑膜膨出和脊柱裂等.研究神经管发育机制及NTD致畸机制对预防畸形发生有一定的意义.Wnt信号通路在神经管发育过程中发挥重要的作用,不但参与了胚胎背腹轴的形成,而且与细胞极性建立、细胞命运决定等多个发育事件有关.阻断Wnt信号途径,动物胚胎会产生明显的突变表型,如果蝇的异常表皮、小鼠腹侧化肢体、线虫EMS细胞丧失不对称分裂等.近来研究发现,Wnt信号通路异常与神经管畸形发生密切相关,Wnt信号通路某一环节发生异常或中断都可能导致畸形的发生.     

肿瘤中雌激素信号转导通路的研究进展

雌激素（estrogen,E₂）可通过特异性结合并激活其受体传递信号,广泛调控机体的各种功能,如生殖功能、骨骼及其它组织的分化和维持等。雌激素受体属于核受体超家族,有3个亚类即雌激素受体α（estrogenreceptorα,ERα）、ERβ和最近发现的G蛋白偶联受体——GPR（G protein-coupled receptor）30/GPER（G protein-coupled estrogen receptor）。典型的ER作     

白血病形成中JAK/STAT信号通路的持续激活

JAK/STAT通路是细胞因子、生长因子、激素等广泛应用的信号转导通路,白血病形成中普遍存在JAK/STAT通路的持续激活。白血病融合蛋白的表达、酪氨酸激酶过度表达或激活突变及某些病毒感染可导致JAK/STAT通路的持续激活和调节异常,并引起细胞的转化和白血病形成。了解白血病形成中JAK/STAT通路的异常调节有助于开发靶向JAK/STAT通路的治疗策略。