Search | Engineering

订阅投稿

首页工程期刊工程焦点工程成就工程前沿关于我们 English

资源类型

期刊论文 6

年份

2023 1

2021 2

2018 1

2017 1

2016 1

关键词

亮氨酸 1

低蛋白日粮 1

成年大鼠 1

生长性能 1

肌肉重量 1

蛋白质合成 1

展开︾

检索范围：

排序：展示方式：

FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression

《医学前沿（英文）》 2023年第17卷第4期页码 714-728 doi: 10.1007/s11684-022-0959-5

摘要： FRMD6, a member of the 4.1 ezrin–radixin–moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^−/− gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

关键词： FRMD6 lung cancer mTOR pathway

HTML PDF 收藏

mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?

Shi-Yong Sun

《医学前沿（英文）》 2021年第15卷第2期页码 221-231 doi: 10.1007/s11684-020-0812-7

摘要： The mammalian target of rapamycin (mTOR) critically regulates several essential biological functions, such as cell growth, metabolism, survival, and immune response by forming two important complexes, namely, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). mTOR signaling is often dysregulated in cancers and has been considered an attractive cancer therapeutic target. Great efforts have been made to develop efficacious mTOR inhibitors, particularly mTOR kinase inhibitors, which suppress mTORC1 and mTORC2; however, major success has not been achieved. With the strong scientific rationale, the intriguing question is why cancers are insensitive or not responsive to mTOR-targeted cancer therapy in clinics. Beyond early findings on induced activation of PI3K/Akt, MEK/ERK, and Mnk/eIF4E survival signaling pathways that compromise the efficacy of rapalog-based cancer therapy, recent findings on the essential role of GSK3 in mediating cancer cell response to mTOR inhibitors and mTORC1 inhibition-induced upregulation of PD-L1 in cancer cells may provide some explanations. These new findings may also offer us the opportunity to rationally utilize mTOR inhibitors in cancer therapy. Further elucidation of the biology of complicated mTOR networks may bring us the hope to develop effective therapeutic strategies with mTOR inhibitors against cancer.

关键词： mTOR cancer therapy resistance GSK3 protein degradation E3 ubiquitin ligase PD-L1

HTML PDF 收藏

Prohibitin regulates mTOR pathway via interaction with FKBP8

Jiahui Zhang, Yanan Yin, Jiahui Wang, Jingjing Zhang, Hua Liu, Weiwei Feng, Wen Yang, Bruce Zetter, Yingjie Xu

《医学前沿（英文）》 2021年第15卷第3期页码 448-459 doi: 10.1007/s11684-020-0805-6

摘要： The ability of tumor cells to sustain continuous proliferation is one of the major characteristics of cancer. The activation of oncogenes and the mutation or inactivation of tumor suppressor genes ensure the rapid proliferation of tumor cells. The PI3K–Akt–mTOR axis is one of the most frequently modified signaling pathways whose activation sustains cancer growth. Unsurprisingly, it is also one of the most commonly attempted targets for cancer therapy. FK506 binding protein 8 (FKBP8) is an intrinsic inhibitor of mTOR kinase that also exerts an anti-apoptotic function. We aimed to explain these contradictory aspects of FKBP8 in cancer by identifying a “switch” type regulator. We identified through immunoprecipitation–mass spectrometry-based proteomic analysis that the mitochondrial protein prohibitin 1 (PHB1) specifically interacts with FKBP8. Furthermore, the downregulation of PHB1 inhibited the proliferation of ovarian cancer cells and the mTOR signaling pathway, whereas the FKBP8 level in the mitochondria was substantially reduced. Moreover, concomitant with these changes, the interaction between FKBP8 and mTOR substantially increased in the absence of PHB1. Collectively, our finding highlights PHB1 as a potential regulator of FKBP8 because of its subcellular localization and mTOR regulating role.

关键词： prohibitin 1 FKBP8 mTOR cell proliferation cancer

HTML PDF 收藏

Resveratrol reduces intracellular reactive oxygen species levels by inducing autophagy through the AMPK-mTOR

Jun Song, Yeping Huang, Wenjian Zheng, Jing Yan, Min Cheng, Ruxing Zhao, Li Chen, Cheng Hu, Weiping Jia

《医学前沿（英文）》 2018年第12卷第6期页码 697-706 doi: 10.1007/s11684-018-0655-7

摘要：

Oxidative stress induced by free fatty acid aggravates endothelial injury, which leads to diabetic cardiovascular complications. Reduction of intracellular oxidative stress may attenuate these pathogenic processes. The dietary polyphenol resveratrol reportedly exerts potential protective effects against endothelial injury. This study determined whether resveratrol can reduce the palmitic acid (PA)-induced generation of reactive oxygen species (ROS) and further explored the underlying molecular mechanisms. We found that resveratrol significantly reduced the PA-induced endothelial ROS levels in human aortic endothelial cells. Resveratrol also induced endothelial cell autophagy, which mediated the effect of resveratrol on ROS reduction. Resveratrol stimulated autophagy via the AMP-activated protein kinase (AMPK)-mTOR pathway. Taken together, these data suggest that resveratrol prevents PA-induced intracellular ROS by autophagy regulation via the AMPK-mTOR pathway. Thus, the induction of autophagy by resveratrol may provide a novel therapeutic candidate for cardioprotection in metabolic syndrome.

关键词： resveratrol reactive oxygen species AMPK mTOR autophagy

HTML PDF 收藏

Autophagy and the nutritional signaling pathway

Long HE,Shabnam ESLAMFAM,Xi MA,Defa LI

《农业科学与工程前沿（英文）》 2016年第3卷第3期页码 222-230 doi: 10.15302/J-FASE-2016106

摘要： During their growth and development, animals adapt to tremendous changes in order to survive. These include responses to both environmental and physiological changes and autophagy is one of most important adaptive and regulatory mechanisms. Autophagy is defined as an autolytic process to clear damaged cellular organelles and recycle the nutrients via lysosomic degradation. The process of autophagy responds to special conditions such as nutrient withdrawal. Once autophagy is induced, phagophores form and then elongate and curve to form autophagosomes. Autophagosomes then engulf cargo, fuse with endosomes, and finally fuse with lysosomes for maturation. During the initiation process, the ATG1/ULK1 (unc-51-like kinase 1) and VPS34 (which encodes a class III phosphatidylinositol (PtdIns) 3-kinase) complexes are critical in recruitment and assembly of other complexes required for autophagy. The process of autophagy is regulated by autophagy related genes (ATGs). Amino acid and energy starvation mediate autophagy by activating mTORC1 (mammalian target of rapamycin) and AMP-activated protein kinase (AMPK). AMPK is the energy status sensor, the core nutrient signaling component and the metabolic kinase of cells. This review mainly focuses on the mechanism of autophagy regulated by nutrient signaling especially for the two important complexes, ULK1 and VPS34.

关键词： Autophagy ULK1 complex VPS34 complex AMPK mTOR nutrient signaling

HTML PDF 收藏

低蛋白日粮中添加亮氨酸通过雷帕霉素靶蛋白信号通路增加成年大鼠骨骼肌重量及蛋白质合成

张博, 楚丽翠, 刘宏, 谢春元, 谯仕彦, 曾祥芳

《工程（英文）》 2017年第3卷第5期页码 760-765 doi: 10.1016/J.ENG.2017.03.008

摘要：试验第11天，所有大鼠大剂量一次性腹腔注射L-[ring-2H5]苯丙氨酸注射液，测定血清中的氨基酸含量、比目鱼肌和腓肠肌重量、蛋白质合成速率及mTOR信号通路相关分子的表达。本文结论如下，在成年大鼠长期采食低蛋白日粮的情况下，日粮中添加亮氨酸可以改善大鼠的生长性能，通过提高mTOR通路中S6K1磷酸化水平，促进大鼠骨骼肌蛋白质合成，抑制蛋白质降解。

关键词：低蛋白日粮亮氨酸生长性能肌肉重量蛋白质合成成年大鼠