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https://www.readbyqxmd.com/read/29779034/ras-gtpase-activating-like-protein-iqgap1-iqgap1-promotes-breast-cancer-proliferation-and-invasion-and-correlates-with-poor-clinical-outcomes
#1
Fanye Zeng, Weihua Jiang, Wei Zhao, Yuxiang Fan, Yanhua Zhu, Hongliang Zhang
BACKGROUND Breast cancer is one of the most common female cancers in the world. As a key integrator of cell signaling pathways, IQGAP1 contributes to the development and progression of several cancers. However, the exact effects and molecular mechanisms of IQGAP1 in breast cancer progression remain poorly understood. MATERIAL AND METHODS In the present study, IQGAP1 expression was measured in 96 paired breast cancer samples and the corresponding adjacent non-cancerous tissues by immunohistochemistry and quantitative polymerase chain reaction...
May 20, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29778238/interplay-between-estrogen-related-receptors-and-steroidogenesis-controlling-molecules-in-adrenals-in-vivo-and-in-vitro-study
#2
A Pacwa, E Gorowska-Wojtowicz, A Ptak, P Pawlicki, A Milon, M Sekula, K Lesniak, B Bilinska, A Hejmej, M Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found...
May 16, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29777330/down-regulating-il-6-gp130-targets-improved-the-anti-tumor-effects-of-5-fluorouracil-in-colon-cancer
#3
Sanhong Li, Jilai Tian, Hongming Zhang, Shoubing Zhou, Xiyong Wang, Lei Zhang, Jiapeng Yang, Zhigang Zhang, Zhenling Ji
Recent studies have confirmed that IL-6/GP130 targets are closely associated with tumor growth, metastasis and drug resistance. 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent for colon cancer but is limited due to chemoresistance and high cytotoxicity. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator, was discovered by multiple ligand simultaneous docking and drug repositioning approaches to have a novel function as an IL-6/GP130 target inhibitor. Thus, we speculated that in colon cancer, the anti-tumor efficacy of 5-FU might be increased in combination with IL-6/GP130 inhibitors...
May 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29775418/prolonged-activation-of-camp-signaling-leads-to-endothelial-barrier-disruption-via-transcriptional-repression-of-rras
#4
Carole Y Perrot, Junko Sawada, Masanobu Komatsu
The increase in cAMP levels in endothelial cells triggers cellular signaling to alter vascular permeability. It is generally considered that cAMP signaling stabilizes the endothelial barrier function and reduces permeability. However, previous studies have only examined the permeability shortly after cAMP elevation and thus have only investigated acute responses. Because cAMP is a key regulator of gene expression, elevated cAMP may have a delayed but profound impact on the endothelial permeability by altering the expression of the genes that are vital for the vessel wall stability...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29774215/importance-of-functional-loss-of-fus-in-ftld-als
#5
REVIEW
Shinsuke Ishigaki, Gen Sobue
Fused in sarcoma (FUS) is an RNA binding protein that regulates RNA metabolism including alternative splicing, transcription, and RNA transportation. FUS is genetically and pathologically involved in frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis (ALS). Multiple lines of evidence across diverse models suggest that functional loss of FUS can lead to neuronal dysfunction and/or neuronal cell death. Loss of FUS in the nucleus can impair alternative splicing and/or transcription, whereas dysfunction of FUS in the cytoplasm, especially in the dendritic spines of neurons, can cause mRNA destabilization...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29774109/sik2-attenuates-proliferation-and-survival-of-breast-cancer-cells-with-simultaneous-perturbation-of-mapk-and-pi3k-akt-pathways
#6
Neslihan Zohrap, Özge Saatci, Burcak Ozes, Ipek Coban, Hasan Murat Atay, Esra Battaloglu, Özgür Şahin, Kuyas Bugra
Salt Inducible Kinase2 (SIK2) has been shown to contribute to tumorigenesis in multiple tumor types in a dichotomous manner. However, little is known about its contribution to breast malignancies. Here, we report SIK2 as a potential tumor suppressor in breast cancer whose expression was reduced in tumor tissues and breast cancer cell lines compared to normal counterparts. In vitro loss- and gain-of-function experiments combined with xenograft studies demonstrated that SIK2-mediated attenuation of proliferation and survival of breast cancer cells with parallel inhibition of both Ras/Erk and PI3K/Akt pathways...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#7
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29769411/knockdown-of-rab7a-suppresses-the-proliferation-migration-and-xenograft-tumor-growth-of-breast-cancer-cells
#8
Jiming Xie, Yan Yan, Fang Liu, Hongbin Kang, Fengying Xu, Weili Xiao, Haiyan Wang, Yuzhen Wang
Breast cancer is a common invasive cancer in women. Ras-related protein Rab-7a (Rab7a) is involved in late endocytic trafficking, while its role in breast cancer is largely unclear. In this study, we investigated the role of Rab7a in breast cancer. Comparing with adjacent breast tissues, Rab7a expression was increased in breast cancer tissues. Using lentivirus-mediated knockdown strategy, we found that Rab7a silencing inhibited the proliferation and colony formation of MDA-MB-231 cells. Apoptosis and G2 cell cycle arrest were induced in Rab7a knockdown...
May 16, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29769200/long-chain-n-3-fatty-acids-attenuate-oncogenic-kras-driven-proliferation-by-altering-plasma-membrane-nanoscale-proteolipid-composition
#9
Natividad R Fuentes, Mohamed Mlih, Rola Barhoumi, Yang-Yi Fan, Paul Hardin, Trevor J Steele, Spencer Behmer, Ian A Prior, Jason Karpac, Robert S Chapkin
Ras signaling originates from transient nanoscale compartmentalized regions of the plasma membrane composed of specific proteins and lipids. The highly specific lipid composition of these nanodomains, termed nanoclusters, facilitates effector recruitment and therefore influences signal transduction. This suggests that Ras nanocluster proteolipid composition could represent a novel target for future chemoprevention interventions. There is evidence that consumption of fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17) and docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19) may reduce colon cancer risk in humans, yet the mechanism underlying this effect is unknown...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29767389/high-expression-of-abl2-suppresses-apoptosis-in-gastric-cancer
#10
Yun Liu, Chen Shao, Linqi Zhu, Sihong Jiang, Guanlin Li, Wei Zhang, Yajing Lin, Ying Ni, Hui Cao, Shihe Shao
BACKGROUND: Diseases associated with Abelson-related gene (also called ABL2) include leukemia; furthermore, previous researches have studied the expressions and functions of ABL2 in different types of malignancies and found that it plays an important role in almost all kinds of cancers. AIMS: Nevertheless, the mechanism of ABL2 in gastric cancer (GC) remains vague. METHODS: In the present study, the level of ABL2 in human GC tissues was detected by immunohistochemistry...
May 16, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29765906/epstein-barr-virus-and-human-papillomaviruses-interactions-and-their-roles-in-the-initiation-of-epithelial-mesenchymal-transition-and-cancer-progression
#11
REVIEW
Farhan S Cyprian, Halema F Al-Farsi, Semir Vranic, Saghir Akhtar, Ala-Eddin Al Moustafa
Oncoviruses are implicated in around 20% of all human cancers including both solid and non-solid malignancies. Epstein-Barr virus (EBV) and human papillomaviruses (HPVs) are the most common oncoviruses worldwide. Currently, it is well established that onco-proteins of EBV (LMP1, LMP2A, and EBNA1) and high-risk HPVs (E5 and E6/E7) play an important role in the initiation and/or progression of several human carcinomas, including cervical, oral, and breast. More significantly, it has been recently pointed out that viral onco-proteins of EBV and high-risk HPVs can be co-present and consequently cooperate to initiate and/or amplify epithelial-mesenchymal transition (EMT), which is the hallmark of cancer progression and metastasis...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29765155/genetic-transcriptional-and-post-translational-regulation-of-the-programmed-death-protein-ligand-1-in-cancer-biology-and-clinical-correlations
#12
REVIEW
Ioannis Zerdes, Alexios Matikas, Jonas Bergh, George Z Rassidakis, Theodoros Foukakis
The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1...
May 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29764501/eya4-inhibits-hepatocellular-carcinoma-growth-and-invasion-by-suppressing-nf-%C3%AE%C2%BAb-dependent-rap1-transactivation
#13
Shi-Jing Mo, Xun Hou, Xiao-Yi Hao, Jian-Peng Cai, Xin Liu, Wei Chen, Dong Chen, Xiao-Yu Yin
BACKGROUND: Our previous studies demonstrated that eyes absent homolog 4 (EYA4), a member of the eye development-related EYA family in Drosophila, is frequently methylated and silenced in hepatocellular carcinoma (HCC) specimens and associated with shorter survival. The current work aimed to explore the mechanisms through which EYA4 functions as a tumor suppressor in HCC. METHODS: Stable EYA4-expressing plasmid (pEYA4) transfectants of the human HCC cell lines Huh-7 and PLC/PRF/5 (PLC) were established...
April 3, 2018: Cancer communications
https://www.readbyqxmd.com/read/29760808/piasy-antagonizes-ras-driven-nsclc-survival-by-promoting-gata2-sumoylation
#14
Bin Chen, Jie Luo, Yirui Zhou, Xu Xin, Rong Cai, Chunhua Ling
GATA2 regulated transcriptional network has been validated requisite for RAS oncogene-driven non-small cell lung cancer (NSCLC). GATA2 has been reported as a SUMOylated protein. In endothelial cells, its transcriptional activity is attenuated by SUMO-2 conjugation, which is specifically catalyzed by its E3 ligase PIASy. In this study, we found a decreased expression of PIASy in RAS mutant NSCLC cell lines and specimens with RAS mutations. Forced expression of PIASy in NSCLC cells inhibits their viability in vitro , as well as tumorigenesis and growth in vivo ...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29760662/targeting-renin-angiotensin-system-against-alzheimer-s-disease
#15
REVIEW
Abadi Kahsu Gebre, Birhanetensay Masresha Altaye, Tesfay Mehari Atey, Kald Beshir Tuem, Derbew Fikadu Berhe
Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer's disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29760449/aurora-kinase-a-aurka-interaction-with-wnt-and-ras-mapk-signalling-pathways-in-colorectal-cancer
#16
Annika Jacobsen, Linda J W Bosch, Sanne R Martens-de Kemp, Beatriz Carvalho, Anke H Sillars-Hardebol, Richard J Dobson, Emanuele de Rinaldis, Gerrit A Meijer, Sanne Abeln, Jaap Heringa, Remond J A Fijneman, K Anton Feenstra
Hyperactivation of Wnt and Ras-MAPK signalling are common events in development of colorectal adenomas. Further progression from adenoma-to-carcinoma is frequently associated with 20q gain and overexpression of Aurora kinase A (AURKA). Interestingly, AURKA has been shown to further enhance Wnt and Ras-MAPK signalling. However, the molecular details of these interactions in driving colorectal carcinogenesis remain poorly understood. Here we first performed differential expression analysis (DEA) of AURKA knockdown in two colorectal cancer (CRC) cell lines with 20q gain and AURKA overexpression...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29758119/loss-of-protein-phosphatase-6-in-mouse-keratinocytes-enhances-k-ras-g12d-driven-tumor-promotion
#17
Koreyuki Kurosawa, Yui Inoue, Yoichiro Kakugawa, Yoji Yamashita, Kosuke Kanazawa, Kazuhiro Kishimoto, Miyuki Nomura, Yuki Momoi, Ikuro Sato, Natsuko Chiba, Mai Suzuki, Honami Ogoh, Hidekazu Yamada, Koh Miura, Toshio Watanabe, Nobuhiro Tanuma, Masahiro Tachi, Hiroshi Shima
Here, we address the function of protein phosphatase 6 (PP6) loss on K-ras-initiated tumorigenesis in keratinocytes. To do so, we developed tamoxifen-inducible double mutant (K-rasG12D -expressing and Ppp6c-deficient) mice in which K-rasG12D expression is driven by the cytokeratin 14 (K14) promoter. Doubly-mutant mice showed early onset tumor formation in lip, nipples, external genitalia, anus and palms, and had to be sacrificed by three weeks after induction by tamoxifen, while comparably-treated K-rasG12D -expressing mice did not...
May 14, 2018: Cancer Science
https://www.readbyqxmd.com/read/29757658/a-macropinocytosis-intensifying-albumin-domain-based-scfv-antibody-and-its-conjugate-directed-against-k-ras-mutant-pancreatic-cancer
#18
Xiaofei Wang, Weijin Sheng, Yangyang Wang, Liang Li, Yi Li, Shenghua Zhang, Xiujun Liu, Shuzhen Chen, Yongsu Zhen
Enhanced macropinocytosis has been found in K-Ras mutant pancreatic cancer cells and through which albumin can massively enter into the K-Ras driven cancer cells suggesting its role serving as micropinocytosis-intensifying drug delivery carrier. In the present study, a novel recombinant protein Fv-LDP-D3 and its reconstituted analogue Fv-LDP-D3-AE were designed and prepared. In which, Fv is the fragment of an anti-EGFR antibody, D3 is the domain III of HSA, LDP is the apoprotein of the antitumor antibiotic lidamycin (LDM), and AE is an extremely cytotoxic enediyne derived from LDM...
May 14, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29755114/az304-a-novel-dual-braf-inhibitor-exerts-anti-tumour-effects-in-colorectal-cancer-independently-of-braf-genetic-status
#19
Rui Ma, Ling Xu, Xiujuan Qu, Xiaofang Che, Ye Zhang, Yibo Fan, Ce Li, Tianshu Guo, Kezuo Hou, Xuejun Hu, Lisa Drew, Minhui Shen, Tony Cheung, Yunpeng Liu
BACKGROUND: BRAF mutation is associated with poor clinical outcome of patients with malignant tumours, and mediates resistance to chemotherapy and targeted therapy. This study aimed to determine whether V600E mutant and wild type BRAF colorectal cancers exhibit distinct sensitivities to the dual BRAF inhibitor AZ304. METHODS: Kinase activity was assessed by the AlphaScreen assay. Then, MTT assay, EdU assay, colony-formation assay and Western blot were performed to evaluate the anti-tumour effects of AZ304 in vitro...
May 14, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29754503/hesperidin-suppresses-renin-angiotensin-system-mediated-nox2-over-expression-and-sympathoexcitation-in-2k-1c-hypertensive-rats
#20
Chutamas Wunpathe, Prapassorn Potue, Putcharawipa Maneesai, Sarawoot Bunbupha, Parichat Prachaney, Upa Kukongviriyapan, Veerapol Kukongviriyapan, Poungrat Pakdeechote
Hesperidin, a flavonoid derived from citrus fruits, possesses several beneficial effects including anti-oxidation and anti-inflammation. The aim of this study was to investigate the effects of hesperidin on the renin-angiotensin system (RAS) cascade that mediated oxidative stress and sympathoexcitation in two-kidney, one-clipped (2K-1C) hypertensive rats. 2K-1C hypertension was induced in male Sprague-Dawley rats. Hypertensive rats were treated with hesperidin at 20[Formula: see text]mg/kg or 40[Formula: see text]mg/kg or losartan at 10[Formula: see text]mg/kg beginning at three weeks after surgery and then continued for four weeks ([Formula: see text]/group)...
May 13, 2018: American Journal of Chinese Medicine
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