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Mtor akt independent

Meng Xu, Huamao Jaing, Haiguang Wang, Jiajie Liu, Baohao Liu, Zhongqiang Guo
The mechanisms of malignant cell metastasis to secondary sites are complex and multifactorial. Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis. SIBLINGs promote malignant cell invasion and metastasis by enhancing matrix metalloproteinase 2 (MMP‑2) and MMP‑9 expression. Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells...
June 18, 2018: Oncology Reports
Ananda Mukherjee, Amanda L Patterson, Jitu W George, Tyler J Carpenter, Zachary B Madaj, Galen Hostetter, John I Risinger, Jose M Teixeira
Endometrial adenocarcinoma (EndoCA) is the most common gynecological cancer type in the US, and its incidence is increasing. The majority of patients are disease-free after surgical resection of stage I tumors, which is often followed by radiation therapy, but most patients with advanced disease recur and have a poor prognosis, largely because the tumors become refractory to cytotoxic chemotherapies. PTEN, a commonly mutated tumor suppressor in EndoCAs, is well known for its ability to inhibit the AKT/mTOR signaling pathway...
June 13, 2018: Molecular Cancer Therapeutics
Lichen Xing, Leiming Zhang, Yali Feng, Zhe Cui, Lin Ding
Retinoblastoma (RB) is the most common intraocular malignancy in infants and children with high mortality rate in developing countries. Emerging evidence demonstrated that abnormally expressed circular RNAs (circRNAs) are involved in tumorigenesis and progression in several malignancies. However, their clinical values, biological functions and mechanisms in RB has not been reported before. Recently, hsa_circ_0001649 was found to play imperative roles in cholangiocarcinoma, gastric cancer, and hepatocellular carcinoma...
June 1, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yihui Yu, Zuoying Hu, Bing Li, Zhimei Wang, Shaoliang Chen
This study aimed to investigate the effects and molecular mechanisms of ivabradine in preventing cardiac hypertrophy in an established transverse aortic constriction (TAC) mouse model. A total of 56 male C57BL/6 mice were randomly assigned into the following seven groups (8 mice per group): sham, TAC model, Iva-10 (10 mg/kg/day ivabradine), Iva-20 (20 mg/kg/day ivabradine), Iva-40 (40 mg/kg/day ivabradine), Iva-80 (80 mg/kg/day ivabradine), and Rap (rapamycin, a positive control). Echocardiography and left ventricular hemodynamics were performed...
May 22, 2018: Molecular and Cellular Biochemistry
Dina Mönch, Sabine Bode-Erdmann, Jörg Kalla, Jörn Sträter, Carsten Schwänen, Roger Falkenstern-Ge, Siegfried Klumpp, Godehard Friedel, German Ott, Claudia Kalla
Malignant pleural mesothelioma (MPM) is a neoplasm with inferior prognosis and notorious chemotherapeutic resistance. Targeting aberrantly overexpressed kinases to cure MPM is a promising therapeutic strategy. Here, we examined ALK, MET and mTOR as potential therapeutic targets and determined the combinatorial efficacy of ALK and mTOR targeting on tumor cell growth in vivo . First, ALK overexpression, rearrangement and mutation were studied in primary MPM by qRT-PCR, FISH, immunohistochemistry and sequence analysis; mTOR and MET expression by qRT-PCR and immunohistochemistry...
April 17, 2018: Oncotarget
Aurelia Lamanuzzi, Ilaria Saltarella, Vanessa Desantis, Maria Antonia Frassanito, Patrizia Leone, Vito Racanelli, Beatrice Nico, Domenico Ribatti, Paolo Ditonno, Marcella Prete, Antonio Giovanni Solimando, Francesco Dammacco, Angelo Vacca, Roberto Ria
The mammalian Target of Rapamycin (mTOR) is an intracellular serine/threonine kinase that mediates intracellular metabolism, cell survival and actin rearrangement. mTOR is made of two independent complexes, mTORC1 and mTORC2, activated by the scaffold proteins RAPTOR and RICTOR, respectively. The activation of mTORC1 triggers protein synthesis and autophagy inhibition, while mTORC2 activation promotes progression, survival, actin reorganization, and drug resistance through AKT hyper-phosphorylation on Ser473...
April 17, 2018: Oncotarget
Ji-Eun Kim, Ah-Reum Ko, Hye-Won Hyun, Su-Ji Min, Tae-Cheon Kang
Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE...
May 10, 2018: Cell Death & Disease
Xiaoxiao Wang, Xin Cao, Ruifang Sun, Charlene Tang, Alexandar Tzankov, Jun Zhang, Ganiraju C Manyam, Min Xiao, Yi Miao, Kausar Jabbar, Xiaohong Tan, Yuyang Pang, Carlo Visco, Yan Xie, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L Richards, Eric D Hsi, William W L Choi, J Han van Krieken, Jooryung Huh, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Ben M Parsons, Jane N Winter, Miguel A Piris, Shaoying Li, Roberto N Miranda, L Jeffrey Medeiros, Yong Li, Zijun Y Xu-Monette, Ken H Young
PTEN loss has been associated with poorer prognosis in many solid tumors. However, such investigation in lymphomas is limited. In this study, PTEN cytoplasmic and nuclear expression, PTEN gene deletion, and PTEN mutations were evaluated in two independent cohorts of diffuse large B-cell lymphoma (DLBCL). Cytoplasmic PTEN expression was found in approximately 67% of total 747 DLBCL cases, more frequently in the activated B-cell-like subtype. Nuclear PTEN expression was less frequent and at lower levels, which significantly correlated with higher PTEN mRNA expression...
June 2018: Neoplasia: An International Journal for Oncology Research
Flávia Sayuri Matsuo, Marília Ferreira Andrade, Adriano Mota Loyola, Sindeval José da Silva, Marcelo José Barbosa Silva, Sérgio Vitorino Cardoso, Paulo Rogério de Faria
Phosphatidylinositol-3-kinases are kinases that lead to AKT phosphorylation and thus mTOR and GSK3β activation. These proteins are linked to tumorigenesis, but their roles in driving cervical lymph node (CLN) metastasis of oral squamous cell carcinoma (OSCC) cells are unknown. This study aimed to investigate the role of AKT, mTOR, and GSK3β proteins in the occurrence of CLN metastasis in OSCC patients. Ninety and 18 paraffin-embedded OSCC and oral mucosa samples were included, respectively. We divided our OSCC patients into non-metastasizing (PNM) and metastasizing (PM) groups, and the expression of total AKT, pAKT1Thr308 , pAKTSer473 , GSK3β, pGSK3βSer9 , and pmTORSer2448 was analyzed by immunohistochemistry...
June 2018: Virchows Archiv: An International Journal of Pathology
Shota Yamazaki, Youichi Higuchi, Masayuki Ishibashi, Hiroko Hashimoto, Masahiro Yasunaga, Yasuhiro Matsumura, Katsuya Tsuchihara, Masahiro Tsuboi, Koichi Goto, Atsushi Ochiai, Genichiro Ishii
Primary resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a serious problem in lung adenocarcinoma patients harboring EGFR mutations. The aim of this study was to examine whether and how collagen type I (Col I), the most abundantly deposited matrix in tumor stroma, affects EGFR-TKI sensitivity in EGFR-mutant cells. We evaluated the EGFR-TKI sensitivity of EGFR-mutated cancer cells cultured with Col I. Changes in the activation of downstream signaling molecules of EGFR were analyzed...
June 2018: Cancer Science
Yosif El-Darawish, Wen Li, Kyosuke Yamanishi, Magdalena Pencheva, Naoto Oka, Hiromichi Yamanishi, Tomohiro Matsuyama, Yoshimasa Tanaka, Nagahiro Minato, Haruki Okamura
Combined stimulation by IL-2 and IL-18 effectively promotes proliferation of NK cells, whereas singular stimulation does not. In this study, synergistic effects of these cytokines on NK cells proliferation was analyzed, focusing on the roles of IL-18. In splenic resting NK cells from IL-18KO mice, IL-18 rapidly activated NF-κB independently of IL-2, and activated or up-regulated various molecules downstream of PI3K/AKT and mTOR, including S6, Bcl-XL, ATG5, and LC3II, accompanying increases in cell growth and survival...
March 30, 2018: Journal of Leukocyte Biology
Ramón García-Escudero, Carmen Segrelles, Marta Dueñas, María Pombo, Claudio Ballestín, Marina Alonso-Riaño, Pablo Nenclares, Roberto Álvarez-Rodríguez, Gregorio Sánchez-Aniceto, Ana Ruíz-Alonso, José Luis López-Cedrún, Jesús M Paramio, Corina Lorz
OBJECTIVES: Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved...
April 2018: Oral Oncology
Yen-Hsiu Yeh, Ho-Fu Hsiao, Yen-Cheng Yeh, Tien-Wen Chen, Tsai-Kun Li
BACKGROUND: Tumor microenvironments (TMEs) activate various axes/pathways, predominantly inflammatory and hypoxic responses, impact tumorigenesis, metastasis and therapeutic resistance significantly. Although molecular pathways of individual TME are extensively studied, evidence showing interaction and crosstalk between hypoxia and inflammation remain unclear. Thus, we examined whether interferon (IFN) could modulate both inflammatory and hypoxic responses under normoxia and its relation with cancer development...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
Prabhakaran Kumar, Alejandra Marinelarena, Divya Raghunathan, Vandhana K Ragothaman, Shikha Saini, Palash Bhattacharya, Jilao Fan, Alan L Epstein, Ajay V Maker, Bellur S Prabhakar
Regulatory T cells (Tregs) play a pivotal role in immune-tolerance, and loss of Treg function can lead to the development of autoimmunity. Natural Tregs generated in the thymus substantially contribute to the Treg pool in the periphery, where they suppress self-reactive effector T cells (Teff) responses. Recently, we showed that OX40L (TNFSF4) is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation (CAP-independent) in the presence of low-dose IL-2. Therefore, we hypothesized that OX40 signaling might be integral to the TCR-independent phase of murine and human thymic Treg (tTreg) development...
March 26, 2018: Cellular & Molecular Immunology
Yong Guo, Qing Qing Shan, Ping Yu Gong, Sen Chun Wang
Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is triggered by BCR/ABL tyrosine kinase which activates the downstream signaling pathways, such as Akt/mTOR, RAF/MEK/ERK, and STAT5 pathways. Curcumin has been shown to have inhibitory effects on cancers by inducing apoptosis and autophagy. We demonstrated that curcumin inhibited activation of Akt-mTOR, ABL/STAT5 pathways, inhibited cell proliferation, and induced apoptosis in Ph + ALL cells. Experiments here, were conducted to determine whether autophagy via MEK/ERK pathway involved in anti-leukemia effect of curcumin in Ph + ALL...
2018: Journal of Cancer Research and Therapeutics
Krzysztof Wrzesinski, Stephen J Fey
The recovery of physiological functionality, which is commonly seen in tissue mimetic three-dimensional (3D) cellular aggregates (organoids, spheroids, acini, etc.), has been observed in cells of many origins (primary tissues, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and immortal cell lines). This plurality and plasticity suggest that probably several basic principles promote this recovery process. The aim of this study was to identify these basic principles and describe how they are regulated so that they can be taken in consideration when micro-bioreactors are designed...
March 7, 2018: Bioengineering
Ying Chen, Zeyu Sun, Mei Qi, Xiao Wang, Weifang Zhang, Chunyan Chen, Juan Liu, Weiming Zhao
Cervical cancer continues to be among the most frequent gynaecologic cancers worldwide. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway is constitutively activated in cervical cancer. Inositol polyphosphate 4-phosphatase type II (INPP4B) is a phosphoinositide phosphatase and considered a negative regulatory factor of the PI3K/AKT pathway. INPP4B has diverse roles in various tumours, but its role in cervical cancer is largely unknown. In this study, we investigated the role of INPP4B in cervical cancer...
May 2018: Journal of Cellular and Molecular Medicine
An-Lie Cai, Wei Zeng, Wei-Liang Cai, Jing-Ling Liu, Xue-Wen Zheng, Ying Liu, Xiang-Cheng Yang, Yi Long, Jie Li
Osteosarcoma is characterized by high propensity for metastasis, especially to the lung, which is the main cause of death. Peroxiredoxin-1 (PRDX1) plays significant roles in multiple processes of initiation and progression of tumorogenesis. However, whether PRDX1 participates in metastasis of osteosarcoma remains unknown. Here, we demonstrate that PRDX1 overexpressed in osteosarcoma tissues comparing to adjacent non-tumor tissues. Two independent cohorts of patients showed high level of PRDX1 correlated with clinicopathological features such as larger tumor size and advanced tumor metastasis stage...
February 2, 2018: Oncotarget
Ning Wu, Zunguo Du, Yongjun Zhu, Yang Song, Liewen Pang, Zhiming Chen
The abnormal phosphatase and tensin homolog expression and activated phosphoinositide-3 kinase/Protein kinase B (AKT)/mammalian target of rapamycin signaling pathway are involved in the progression of esophageal squamous cell carcinoma. By assessing the expression pattern of key components in the phosphoinositide-3 kinase/AKT/mammalian target of rapamycin signaling pathway by immunohistochemistry in tumor and nontumor esophageal mucosa from patients with esophageal squamous cell carcinomas, we aimed to carefully explore the relationship between the various protein expressions and clinicopathological factors, as well as patient outcome...
January 1, 2018: Technology in Cancer Research & Treatment
Matthew A Ingersoll, Yu-Wei Chou, Jamie S Lin, Ta-Chun Yuan, Dannah R Miller, Yan Xie, Yaping Tu, Rebecca E Oberley-Deegan, Surinder K Batra, Ming-Fong Lin
Metastatic castration-resistant (CR) prostate cancer (PCa) is a lethal disease for which no effective treatment is currently available. p66Shc is an oxidase previously shown to promote androgen-independent cell growth through generation of reactive oxygen species (ROS) and is elevated in clinical PCa and multiple CR PCa cell lines. We hypothesize p66Shc also increases the migratory activity of PCa cells through ROS and investigate the associated mechanism. Using the transwell assay, our study reveals that the level of p66Shc protein correlates with cell migratory ability across several PCa cell lines...
June 2018: Cellular Signalling
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