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Sumera Rizvi, Samantha R Fischbach, Steven F Bronk, Petra Hirsova, Anuradha Krishnan, Renumathy Dhanasekaran, James B Smadbeck, Rory L Smoot, George Vasmatzis, Gregory J Gores
Deregulated Hippo pathway signaling is associated with aberrant activation of the downstream effector yes-associated protein (YAP), an emerging key oncogenic mediator in cholangiocarcinoma (CCA). In our prior work, we have demonstrated that biliary transduction of YAP along with Akt as a permissive factor induces CCA in mice. To further delineate the mechanisms associated with YAP-associated biliary oncogenesis, we have established seven malignant murine cell lines from our YAP-driven murine CCA model. These cells express the CCA markers SRY (Sex Determining Region Y)-Box 9 (SOX9), cytokeratin (CK)-7 and 19 but lack hepatocyte nuclear factor 4 alpha and alpha-smooth muscle actin, markers of hepatocellular carcinoma and cancer-associated fibroblasts, respectively...
January 19, 2018: Oncotarget
Valentina Miano, Giulio Ferrero, Valentina Rosti, Eleonora Manitta, Jamal Elhasnaoui, Giulia Basile, Michele De Bortoli
Estrogen receptor-α (ERα) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal BC phenotype. Recently, we demonstrated that even in absence of ligands ERα (apoERα) binds chromatin sites where it regulates transcription of several protein-coding and lncRNA genes. Noteworthy, apoERα-regulated lncRNAs marginally overlap estrogen-induced transcripts, thus representing a new signature of luminal BC genes. By the analysis of H3K27ac enrichment in hormone-deprived MCF-7 cells, we defined a set of Super Enhancers (SEs) occupied by apoERα, including one mapped in proximity of the DSCAM-AS1 lncRNA gene...
February 16, 2018: International Journal of Molecular Sciences
Matthew A Ingersoll, Yu-Wei Chou, Jamie S Lin, Ta-Chun Yuan, Dannah 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 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...
February 17, 2018: Cellular Signalling
Dorota Szpak, Lahoucine Izem, Dmitriy Verbovetskiy, Dmitry A Soloviev, Valentin P Yakubenko, Elzbieta Pluskota
Atherosclerosis is a complex inflammatory process characterized by monocyte recruitment into the arterial wall, their differentiation into macrophages, and lipid accumulation. Because integrin αM β2 (CD11b/CD18) mediates multiple diverse functions of leukocytes, we examined its role in atherogenesis. αM -/- /ApoE-/- and ApoE-/- mice were fed a control or high fat diet for 3 or 16 wk to induce atherogenesis. Unexpectedly, αM deficiency accelerated development of atherosclerosis in female but not in male mice...
February 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Jinyoung Park, Mi-Sun Kwon, Eunice EunKyeong Kim, Hyunsook Lee, Eun Joo Song
Although approximately 100 deubiquitinating enzymes (DUBs) are encoded in the human genome, very little is known about the DUBs that function in mitosis. Here, we demonstrate that DUB USP35 functions as a mitotic regulator by controlling the protein levels and downstream signaling of Aurora B and the depletion of USP35 eventually leads to several mitotic defects including cytokinesis failures. USP35 binds to and deubiquitinates Aurora B, and inhibits the APC CDH1 -mediated proteasomal degradation of Aurora B, thus maintaining its steady-state levels during mitosis...
February 15, 2018: Nature Communications
Lei Tian, Zhifeng Zhao, Ling Xie, JinPeng Zhu
Gastric cancer is a prevalent cancer and chemotherapy is a main treatment for patients. Docetaxel is commonly used as a chemotherapeutic drug for gastric cancer patients. With the increasing emergence of docetaxel resistance, exploring the mechanism of chemoresistance may improve prognosis of patients. In this study, we found that overexpressed miR-361-5p suppressed chemoresistance to docetaxel of gastric cancer cells (SGC-7901, MKN-28) by decreasing IC 50 values of docetaxel while increasing cell apoptosis rate, especially in docetaxel resistant SGC-7901 cells...
January 12, 2018: Oncotarget
Kosei Hasegawa, Yuji Ikeda, Yuko Kunugi, Akira Kurosaki, Yuichi Imai, Shunsuke Kohyama, Shoji Nagao, Eito Kozawa, Koji Yoshida, Takuya Tsunoda, Yusuke Nakamura, Keiichi Fujiwara
Cancer immunotherapy has now been established as a leading standard therapeutic option in a subset of patients with cancer. In this study, we conducted a phase I dose-escalation trial using a mixture of 5 peptides to vaccinate cervical cancer patients with HLA-A*2402. The primary endpoints were safety and determination of a recommended vaccine dose, and the secondary endpoints were evaluations of immunologic responses and clinical efficacy. All patients had recurrent or persistent disease and had failed to respond to or were intolerant to prior standard chemotherapy...
February 9, 2018: Journal of Immunotherapy
D-Q Chong, J-L Shan, C-S Yang, R Wang, Z-M Du
OBJECTIVE: The aim of this study was to explore FOXM1-related LncRNA 1(FRLnc1) expression level in gastric cancer (GC) and demonstrate its association with the prognosis. PATIENTS AND METHODS: A total of 173 GC patients from Affiliated Hospital of Jining Medical University were enrolled in the study. GC tissue samples were quantified for FRLnc1 expression level using quantitative PCR (qPCR) method. The relevance between FRLnc1 expression and clinicopathological features was determined by x2-test...
January 2018: European Review for Medical and Pharmacological Sciences
Poyil Pratheeshkumar, Sasidharan Padmaja Divya, Sandeep Kumar Parvathareddy, Norah M Alhoshani, Ismail A Al-Badawi, Asma Tulbah, Fouad Al-Dayel, Abdul K Siraj, Khawla S Al-Kuraya
Epithelial ovarian cancer (EOC) is a highly lethal disease with poor prognosis especially in advanced stage tumor. Emerging evidence has reported that aberrant upregulation of FoxM1 and β-catenin are closely associated with aggressiveness of human cancer. However, interplay between these factors in the aggressiveness of EOC is not fully illustrated. In this study, we show that FoxM1 is frequently increased in Middle Eastern EOC and associated with high proliferative index (p = 0.0007) and high grade tumor (p = 0...
January 9, 2018: Oncotarget
Xiao-Feng Lu, De Zeng, Wei-Quan Liang, Chun-Fa Chen, Shu-Ming Sun, Hao-Yu Lin
Forkhead box protein M1(FoxM1) is a member of forkhead superfamily transcription factors. Emerging evidences have progressively contributed to our understanding on a central role of FoxM1 in human cancers. However, perspectives on the function of FoxM1 in breast cancer (BC) remain conflicting, and mostly were from basic research. Here, we explored the expression profile and prognostic values of FoxM1 based on analysis of pooled clinical datasets derived from online accessible databases, including ONCOMINE , Breast Cancer Gene-Expression Miner v4...
January 2, 2018: Oncotarget
Shuguang Cao, Limiao Lin, Xuanping Xia, Hao Wu
Resistance to chemotherapy is a big challenge for treatment of patients with colorectal cancer; however; the mechanism underlying chemoresistance in colorectal cancer cell has not been elucidated. MicroRNAs (miRNAs) are new players in the development of drug chemoresistance. In our study, we indicated that overexpression of miR-761 promoted the sensitivity of colorectal cancer cells to 5-Fluorouracil (5-FU). miR-761 expression was downregulated in colorectal cancer cell lines and tissues. miR-761 expression was lower in patients with low grade than in patients with high grade...
January 2, 2018: Oncotarget
S Amirhossein Tabatabaei-Dakhili, Rodrigo Aguayo-Ortiz, Laura Domínguez, Carlos A Velázquez-Martínez
The FOXM1 protein is a relevant transcription factor involved in cancer cell proliferation. The direct or indirect inhibition of this protein's transcriptional activity by small molecule drugs correlates well with a potentially significant anti-cancer profile, making this macro molecule a promising drug target. There are a few drug molecules reported to interact with (and inhibit) the FOXM1 DNA binding domain (FOXM1-BD), causing downregulation of protein expression and cancer cell proliferation inhibition. Among these drug molecules are the proteasome inhibitor thiostrepton, the former antidiabetic drug troglitazone, and the new FDI-6 molecule...
January 27, 2018: Journal of Molecular Graphics & Modelling
Srividyameena Haridoss, Mladen I Yovchev, Hannah Schweizer, Sabreen Megherhi, Maria Beecher, Joseph Locker, Michael Oertel
Activin A, a multifunctional cytokine, plays an important role in hepatocyte growth suppression and is involved in liver size control. The present study was aimed to determine the cell location of activin A in the normal rat liver microenvironment and the contribution of activin A signaling to the hepatocyte phenotype to obtain insight into molecular mechanisms. Immunohistochemical and in situ hybridization analyses identified hepatocytes as the major activin A-positive cell population in normal liver and identified mast cells as an additional activin A source...
November 2017: Hepatology Communications
Wei-Zhen Liu, Nian Liu
Propofol has been widely used in lung cancer resections. Some studies have demonstrated that the effects of propofol might be mediated by microRNAs (miRNAs). This study aimed to investigate the effects and mechanisms of propofol on lung cancer cells by regulation of miR-1284. A549 cells were treated with different concentrations of propofol, while transfected with miR-1284 inhibitor, si-FOXM1 and their negative controls. Cell viability, migration, invasion, the expression of miR-1284, FOXM1 and epithelial mesenchymal transition (EMT) factors were respectively detected by CCK8, Transwell, qRT-PCR and western blot assays...
February 5, 2018: Oncology Research
Argyrios Sklavos, Theofilos Poutahidis, Alexander Giakoustidis, Kali Makedou, Katerina Angelopoulou, Alexander Hardas, Paola Andreani, Argyro Zacharioudaki, George Saridis, Thomas Goulopoulos, Kalliopi Tsarea, Maria Karamperi, Vassilios Papadopoulos, Vassilios Papanikolaou, Apostolos Papalois, Stavros Iliadis, Satvinder Mudan, Daniel Azoulay, Dimitrios Giakoustidis
Recent evidence has suggested that downregulation of the Wnt/β-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt-1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days...
January 2018: Oncology Letters
Yun-Gil Roh, Mi-Hye Mun, Mi-So Jeong, Won-Tae Kim, Se-Ra Lee, Jin-Woong Chung, Seung Il Kim, Tae Nam Kim, Jong Kil Nam, Sun-Hee Leem
Recurrence is a serious problem in patients with bladder cancer. The hypothesis for recurrence was that the proliferation of drug-resistant cells was reported, and this study focused on drug resistance due to drug efflux. Previous studies have identified FOXM1 as the key gene for recurrence. We found that FOXM1 inhibition decreased drug efflux activity and increased sensitivity to Doxorubicin. Therefore, we examined whether the expression of ABC transporter gene related to drug efflux is regulated by FOXM1...
February 5, 2018: BMB Reports
Ugo Testa, Eleonora Petrucci, Luca Pasquini, Germana Castelli, Elvira Pelosi
Four main histological subtypes of ovarian cancer exist: serous (the most frequent), endometrioid, mucinous and clear cell; in each subtype, low and high grade. The large majority of ovarian cancers are diagnosed as high-grade serous ovarian cancers (HGS-OvCas). TP53 is the most frequently mutated gene in HGS-OvCas; about 50% of these tumors displayed defective homologous recombination due to germline and somatic BRCA mutations, epigenetic inactivation of BRCA and abnormalities of DNA repair genes; somatic copy number alterations are frequent in these tumors and some of them are associated with prognosis; defective NOTCH, RAS/MEK, PI3K and FOXM1 pathway signaling is frequent...
February 1, 2018: Medicines (Basel, Switzerland)
Sifeng Qu, Xinpei Ci, Hui Xue, Xin Dong, Jun Hao, Dong Lin, Pier-Luc Clermont, Rebecca Wu, Colin C Collins, Peter W Gout, Yuzhuo Wang
BACKGROUND: Docetaxel used for first-line treatment of advanced prostate cancer (PCa) is only marginally effective. We previously showed, using the LTL-313H subrenal capsule patient-derived metastatic PCa xenograft model, that docetaxel combined with Aneustat (OMN54), a multivalent plant-derived therapeutic, led to marked synergistic tumour growth inhibition. Here, we investigated the effect of docetaxel+Aneustat on metastasis. METHODS: C4-2 cells were incubated with docetaxel, Aneustat and docetaxel+Aneustat to assess effects on cell migration...
January 30, 2018: British Journal of Cancer
Ziyu Zhang, Yang Zou, Meirong Liang, Yuanting Chen, Yong Luo, Bicheng Yang, Faying Liu, Yunna Qin, Deming He, Feng Wang, Ouping Huang
Suppressor of fused is essential for the maximal activation of Sonic Hedgehog signaling in development and tumorigenesis. However, the role of Sufu in cervical carcinoma remains unknown. Here, we report new findings of Sufu in regulating the epithelial-to-mesenchymal transition through the FoxM1 transcriptional modulation by 14-3-3ζ protein in cervical carcinoma. Sufu is overexpressed in cervical squamous cell carcinoma and its level in clinical tumor tissues is positively correlated with 14-3-3ζ. Functionanlly, siSufu remarkably prevents the cancer cell migration and invasion...
December 26, 2017: Oncotarget
Marianna Halasi, Ben Hitchinson, Binal N Shah, Renáta Váraljai, Irum Khan, Elizaveta V Benevolenskaya, Vadim Gaponenko, Jack L Arbiser, Andrei L Gartel
Honokiol is a natural product and an emerging drug for a wide variety of malignancies, including hematopoietic malignancies, sarcomas, and common epithelial tumors. The broad range of activity of honokiol against numerous malignancies with diverse genetic backgrounds suggests that honokiol is inhibiting an activity that is common to multiple malignancies. Oncogenic transcription factor FOXM1 is one of the most overexpressed oncoproteins in human cancer. Here we found that honokiol inhibits FOXM1-mediated transcription and FOXM1 protein expression...
January 24, 2018: Cell Death & Disease
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