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https://www.readbyqxmd.com/read/29453318/integration-of-distinct-shca-signaling-complexes-promotes-breast-tumor-growth-and-tyrosine-kinase-inhibitor-resistance
#1
Jacqueline R Ha, Ryuhjin Ahn, Harvey W Smith, Valerie Sabourin, Steven Hėbert, Eduardo Cepeda Cañedo, Young Kyuen Im, Claudia Kleinman, William J Muller, Josie Ursini-Siegel
The commonality between most phospho-tyrosine signaling networks is their shared use of adaptor proteins to transduce mitogenic signals. ShcA (SHC1) is one such adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2) and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor tyrosine kinases (RTKs), such as ErbB2, engage the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29443546/akt1-deficiency-diminishes-skeletal-muscle-hypertrophy-by-reducing-satellite-cell-proliferation
#2
Nobuki Moriya, Mitsunori Miyazaki
Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate...
February 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29428729/downregulated-cdkn1c-p57kip2-drives-tumorigenesis-and-associates-with-poor-overall-survival-in-breast-cancer
#3
Zhu Qiu, Yunhai Li, Beilei Zeng, Xiaoqin Guan, Hongzhong Li
CDKN1C, also known as p57kip2, is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKN1C in breast cancer remains obscure. In the present study, we demonstrated that CDKN1C was dramatically downregulated in breast cancer compared with normal tissues by using real-time quantitative polymerase chain reaction, western blot and two public data portals: The Cancer Genome Atlas (TCGA) and Oncomine datasets. Moreover, the expression of CDKN1C was correlated with age and tumor size in the TCGA cohort containing 708 cases of breast cancer...
February 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29416002/ezh2-inhibits-autophagic-cell-death-of-aortic-vascular-smooth-muscle-cells-to-affect-aortic-dissection
#4
Rui Li, Xin Yi, Xiang Wei, Bo Huo, Xian Guo, Cai Cheng, Ze-Min Fang, Jing Wang, Xin Feng, Ping Zheng, Yun-Shu Su, Jackson Ferdinand Masau, Xue-Hai Zhu, Ding-Sheng Jiang
Enhancer of zeste homolog 2 (EZH2), a methyltransferase that di- and tri-methylates lysine-27 of histone H3, largely functions as a transcriptional repressor, and plays a critical role in various kinds of cancers. Here we report a novel function of EZH2 in regulating autophagic cell death (ACD) of vascular smooth muscle cells (VSMCs) that affect aortic dissection (AD). Inhibition of EZH2 activity by UNC1999 or knockdown EZH2 resulted in VSMC loss, while overexpression of EZH2 facilitated VSMC growth, and these effects of EZH2 on VSMCs were independent of proliferation and apoptosis...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29398519/compound-c-enhances-tau-phosphorylation-at-serine396-via-pi3k-activation-in-an-ampk-and-rapamycin-independent-way-in-differentiated-sh-sy5y-cells
#5
Shohreh Majd, Simon Koblar, John Power
Aggregation of hyperphosphorylated tau (p-tau) in the form of neurofibrillary tangles (NFT) is a main hallmark for Alzheimer's disease (AD). Activation of cellular metabolic axis, made of adenosine monophosphate kinase protein kinase (AMPK) and mammalian target of rapamycin (mTOR) have been implicated in generating tau pathology of AD. Thus, blocking either of these two proteins or both, are suggested as the future therapeutic approaches for AD. How and to what level these approaches could be applied, however are not entirely clear...
January 31, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29386088/phosphoglycerate-mutase-1-pgam1-promotes-pancreatic-ductal-adenocarcinoma-pdac-metastasis-by-acting-as-a-novel-downstream-target-of-pi3k-akt-mtor-pathway
#6
Xinlu Liu, Xiaodong Tan, Peng Liu, Yunhao Wu, Songying Qian, Xiaobo Zhang
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors known, with an overall 5-year survival rate of less than 6% due to early local invasion and distant metastasis. Exploring suitable therapeutic targets associated with invasion and metastasis is required for improving the prognosis of PDAC. In this study, we investigated the role of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) in PDAC. PGAM1 expression was examined in tissue samples of 54 PDAC patients using immunohistochemistry, and the correlation between clinicopathological expression and PGAM1 expression was determined...
January 31, 2018: Oncology Research
https://www.readbyqxmd.com/read/29384220/compound-c-induces-protective-autophagy-in-human-cholangiocarcinoma-cells-via-akt-mtor-independent-pathway
#7
Xiaofang Zhao, Guosong Luo, Ying Cheng, Wenjing Yu, Run Chen, Bin Xiao, Yuancai Xiang, Chunhong Feng, Wenguang Fu, Chunyan Duan, Fuli Yao, Xianming Xia, Qinghua Tao, Mei Wei, Rongyang Dai
Compound C, a well-known inhibitor of AMP-activated protein kinase (AMPK), has been reported to exert antitumor activities in some types of cells. Whether compound C can exert antitumor effects in human cholangiocarcinoma (CCA) remains unknown. Here, we demonstrated that compound C is a potent inducer of cell death and autophagy in human CCA cells. Autophagy inhibitors increased the cytotoxicity of compound C towards human CCA cells, as confirmed by increased LDH release and PARP cleavage. It is notable that compound C treatment increased phosphorylated Akt, sustained high levels of phosphorylated p70S6K and decreased mTOR regulated p-ULK1 (ser757)...
January 31, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29382663/long-non-coding-rna-lncshgl-recruits-hnrnpa1-to-suppress-hepatic-gluconeogenesis-and-lipogenesis
#8
Junpei Wang, Weili Yang, Zhenzhen Chen, Ji Chen, Yuhong Meng, Biaoqi Feng, Libo Sun, Lin Dou, Jian Li, Qinghua Cui, Jichun Yang
Mammalian genomes encode a huge number of LncRNAs with unknown functions. This study determined the role and mechanism of a new LncRNA, LncRNA Suppressor of Hepatic Gluconeogenesis and Lipogenesis (LncSHGL), in regulating hepatic glucose/lipid metabolism. In the livers of obese mice and NAFLD patient, the expression levels of mouse LncSHGL and its human homologous LncRNA B4GALT1-AS1 were reduced. Hepatic LncSHGL restoration improved hyperglycemia, insulin resistance and steatosis in obese diabetic mice, whereas hepatic LncSHGL inhibition promoted fasting hyperglycemia and lipid deposition in normal mice...
January 30, 2018: Diabetes
https://www.readbyqxmd.com/read/29357370/parallel-pi3k-akt-and-mtor-inhibition-is-required-to-control-feedback-loops-that-limit-tumor-therapy
#9
Anuja Sathe, Géraldine Chalaud, Immanuel Oppolzer, Kit Yeng Wong, Margarita von Busch, Sebastian C Schmid, Zhichao Tong, Margitta Retz, Juergen E Gschwend, Wolfgang A Schulz, Roman Nawroth
Targeting the PI3K pathway has achieved limited success in cancer therapy. One reason for the disappointing activity of drugs that interfere with molecules that are important player in this pathway is the induction of multiple feedback loops that have been only partially understood. To understand these limitations and develop improved treatment strategies, we comprehensively characterized molecular mechanisms of PI3K pathway signaling in bladder cancer cell lines upon using small molecule inhibitors and RNAi technologies against all key molecules and protein complexes within the pathway and analyzed functional and molecular consequences...
2018: PloS One
https://www.readbyqxmd.com/read/29328491/microrna-let-7a-regulates-cell-autophagy-by-targeting-rictor-in-gastric-cancer-cell-lines-mgc-803-and-sgc-7901
#10
Hao Fan, Mingkun Jiang, Bowen Li, Yu He, Chi Huang, Dakui Luo, Hao Xu, Li Yang, Jundong Zhou
miR-let-7a is the most widely studied miRNA, whose functions have been well-established by scientists in both carcinogenesis and progression of human cancer, including gastric cancer (GC). However, to date there is a lack of information concerning the relationship between miR-let-7a and cellular autophagy. Using western blotting and immunofluorescence, we determined that upregulation of miR-let-7a led to increased cellular autophagic level, whereas miR-let-7a suppression decreased autophagy activity in GC cells...
January 5, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328380/role-of-the-pi3k%C3%A2-akt%C3%A2-mtor-pathway-in-hepatitis-b-virus-infection-and-replication
#11
Kunlun Xiang, Bin Wang
The replication of hepatitis B virus (HBV) may be modulated by a variety of cell signaling pathways, including the phosphatidylinositol 3‑kinase (PI3K)‑RAC‑α serine/threonine‑protein kinase (AKT)‑serine/threonine‑protein kinase mTOR (mTOR) pathway. The aim of the present study was to determine the regulatory effects of this pathway on the infection and replication of HBV. The results indicated that the HBV entry process may activate the AKT pathway, as demonstrated by AKT phosphorylation in HBV natural infection...
January 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29321573/correlation-of-gli1-and-her2-expression-in-gastric-cancer-identification-of-novel-target
#12
Xinyu Shao, Xiaoyi Kuai, Zhi Pang, Liping Zhang, Longyun Wu, Lijuan Xu, Chunli Zhou
HER2 becomes the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab in recent years. However, the usage of this target agent is still limited because of the resistance to trastuzumab or the negative expression of HER2 in tumor tissues. The Gli1 and HER2 both play an important role in the pathogenesis of gastric cancer. However, the correlation of them is still unclear. Here we found Gli1 and HER2 are highly expressed in gastric cancer tissues, and they are positively related...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316844/pi3k-pathway-and-bcl-2-family-clinicopathological-features-in-prostate-cancer
#13
Norelia Torrealba, Gonzalo Rodriguez-Berriguete, Benito Fraile, Gabriel Olmedilla, Pilar Martínez-Onsurbe, Manuel Sánchez-Chapado, Ricardo Paniagua, Mar Royuela
The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathways and Bcl-2 family play a central role in prostate cancer (PC). The aim was to determine influence in the biochemical progression in PC. To evaluate the association between clinic pathological and immunohistochemical variables, Spearman's test was performed. Log-rank test and Kaplan-Meier curves were used for survival comparisons. To explore the correlation of the studied immunohistochemical parameters and the established prognostic variables with biochemical progression, univariate and multivariate Cox proportional Hazard regression analyses were performed...
January 9, 2018: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/29305578/epithelial-cell-adhesion-molecule-overexpression-regulates-epithelial-mesenchymal-transition-stemness-and-metastasis-of-nasopharyngeal-carcinoma-cells-via-the-pten-akt-mtor-pathway
#14
Meng-He Wang, Rui Sun, Xiao-Min Zhou, Mei-Yin Zhang, Jia-Bin Lu, Yang Yang, Li-Si Zeng, Xian-Zi Yang, Lu Shi, Ruo-Wen Xiao, Hui-Yun Wang, Shi-Juan Mai
Epithelial cell adhesion molecule (EpCAM) is known to be highly expressed in a variety of epithelial carcinomas, and it is involved in cell adhesion and proliferation. However, its expression profile and biological function in nasopharyngeal carcinoma (NPC) remains unclear. In this study, higher expression of EpCAM was found in NPC samples compared with non-cancer nasopharyngeal mucosa by qRT-PCR. Additionally, immunohistochemistry (IHC) analysis of NPC specimens from 64 cases showed that high EpCAM expression was associated with metastasis and shorter survival...
January 5, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29228829/vanadium-pentoxide-increased-pten-and-decreased-shp1-expression-in-nk-92mi-cells-affecting-pi3k-akt-mtor-and-ras-mapk-pathways
#15
Francisco Gallardo-Vera, Miguel Tapia-Rodriguez, Daniel Diaz, Teresa Fortoul van der Goes, Luis F Montaño, Erika P Rendón-Huerta
Vanadium is an air pollutant that imparts immunosuppressive effects on NK cell immune responses, in part, by dysregulating interleukin (IL)-2/IL-2R-mediated JAK signaling pathways and inducing apoptosis. The aim of the present study was to evaluate effects of vanadium pentoxide (V2O5) on other IL-2 receptor-mediated signaling pathways, i.e. PI3K-AKT-mTOR and Ras-MAPK. Here, IL-2-independent NK-92MI cells were exposed to different V2O5 doses for 24 h periods. Expression of PI3K, Akt, mTOR, ERK1/2, MEK1, PTEN, SHP1, BAD and phosphorylated forms, as well as caspases-3, -8, -9, BAX and BAK in/on the cells were then determined by flow cytometry...
December 2018: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29228674/the-regulatory-role-of-aberrant-phosphatase-and-tensin-homologue-and-liver-kinase-b1-on-akt-mtor-c-myc-axis-in-pancreatic-neuroendocrine-tumors
#16
Tsung-Ming Chang, Yan-Shen Shan, Pei-Yi Chu, Shih Sheng Jiang, Wen-Chun Hung, Yu-Lin Chen, Hsiu-Chi Tu, Hui-You Lin, Hui-Jen Tsai, Li-Tzong Chen
Pancreatic neuroendocrine tumor (pNET) is an uncommon type of pancreatic neoplasm. Low Phosphatase and Tensin Homologue (PTEN) expression and activation of the mechanistic target of rapamycin (mTOR) pathway have been noted in pNETs, and the former is associated with poor survival in pNET patients. Based on the results of the RADIANT-3 study, everolimus, an oral mTOR inhibitor, has been approved to treat advanced pNETs. However, the exact regulatory mechanism for the mTOR pathway in pNETs remains largely unknown...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228561/enantiomerically-pure-%C3%AE-dipeptide-derivative-induces-anticancer-activity-against-human-hormone-refractory-prostate-cancer-through-both-pi3k-akt-dependent-and-independent-pathways
#17
Mei-Ling Chan, Chia-Chun Yu, Jui-Ling Hsu, Wohn-Jenn Leu, She-Hung Chan, Lih-Ching Hsu, Shih-Ping Liu, Polina M Ivantcova, Özdemir Dogan, Stefan Bräse, Konstantin V Kudryavtsev, Jih-Hwa Guh
The use of peptides that target cancer cells and induce anticancer activities through various mechanisms is developing as a potential anticancer strategy. KUD983, an enantiomerically pure β-dipeptide derivative, displays potent activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells with submicromolar IC50. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217266/auriculasin-induced-ros-causes-prostate-cancer-cell-death-via-induction-of-apoptosis
#18
Hyun-Dong Cho, Ju-Hye Lee, Kwang-Deog Moon, Ki-Hun Park, Mi-Kyung Lee, Kwon-Il Seo
Recent studies have demonstrated that natural agents targeting the accumulation of reactive oxygen species (ROS) that selectively kill, leaving normal cells undamaged, can suppress prostate cancer. Here, we show that auriculasin, derived from Flemingia philippinensis, induces significant cell death and apoptosis via ROS generation in prostate cancer cells. Auriculasin treatment resulted in selective apoptotic cell death in LNCaP prostate cancer cells, characterized by DNA fragmentation, accumulation of sub-G1 cell population, cleavage of poly (ADP-ribose) polymerase (PARP), regulation of Bax/Bcl-2 ratio, increase of cytosolic apoptosis-inducing factor (AIF) and endonuclease G (EndoG), in addition to inhibiting tumor growth in a xenograft mouse model...
December 4, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29208325/inhibitory-effects-of-compound-dmbt-on-hypoxia-induced-vasculogenic-mimicry-in-human-breast-cancer
#19
Shuixian Li, Qianyun Zhang, Lichun Zhou, Yanhui Guan, Shang Chen, Yu Zhang, Xiuzhen Han
Breast cancer is one of the most serious malignant tumors that harm to women's health. Vasculogenic mimicry (VM) is an alternative type of blood supplement independent of endothelial vessels, which refers to the formation of tumor cell-lined vessels and is associated with tumor invasion, metastasis and poor cancer patient prognosis. Prior antiangiogenic therapy just focused on vascular endothelial cells and did not significantly affect VM. DMBT, 6, 6'-bis (2, 3-dimethoxybenzoyl)-a, a-D-trehalose, has shown to have multiple anti-tumor invasion and metastasis activities; however the exact mechanism is not thoroughly elucidated...
December 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29207186/neuroglobin-promotes-the-proliferation-and-suppresses-the-apoptosis-of-glioma-cells-by-activating-the-pi3k-akt-pathway
#20
Bei Zhang, Yong Liu, Yajun Li, Xiao Zhe, Shijun Zhang, Lei Zhang
Our previous study demonstrated that neuroglobin (Ngb) functions as an independent predictive indicator of the prognosis of patients with glioma and promotes cancer cell growth by suppressing apoptosis. However, the understanding of the mechanisms underlying the survival‑enhancing function of Ngb in glioma is limited. In the present study, KEGG PathwayFinder by gene correlation analysis was performed on the R2: Genomics Analysis and Visualization Platform, which revealed a high association between Ngb and the phosphatidylinositol 3‑kinase (PI3K)/AKT pathway using glioma data (GSE4290) from the Gene Expression Omnibus database...
November 22, 2017: Molecular Medicine Reports
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