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FoxM1 AND Cancer

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https://www.readbyqxmd.com/read/28289076/fumarate-mediates-a-chronic-proliferative-signal-in-fumarate-hydratase-inactivated-cancer-cells-by-increasing-transcription-and-translation-of-ferritin-genes
#1
Michael John Kerins, Ajay Vashisht, Benjamin Xi-Tong Liang, Spencer Jordan Duckworth, Brandon John Praslicka, James Akira Wohlschlegel, Aikseng Ooi
Germline mutations of the gene encoding the tricarboxylic acid cycle (TCA cycle) enzyme, fumarate hydratase (FH), cause a hereditary cancer syndrome known as hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC associated tumors harbor biallelic FH inactivation that results in the accumulation of the TCA cycle metabolite, fumarate. Although it is known that the fumarate accumulation can alter cellular signaling, if and how fumarate confers a growth advantage remains unclear. Here we show that fumarate accumulation confers a chronic proliferative signal by disrupting cellular iron signaling...
March 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28281307/integrated-expression-analysis-identifies-transcription-networks-in-mouse-and-human-gastric-neoplasia
#2
Zheng Chen, Mohammed Soutto, Bushra Rahman, Muhammad W Fazili, DunFa Peng, Maria Blanca Piazuelo, Heidi Chen, M Kay Washington, Yu Shyr, Wael El-Rifai
Gastric cancer is a leading cause of cancer-related deaths worldwide. The Tff1 knockout (KO) mouse model develops gastric lesions that include low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinomas. In this study, we used Affymetrix microarrays gene expression platforms for analysis of molecular signatures in the mouse stomach (Tff1-KO (LGD) and Tff1 wild-type (normal)) and human gastric cancer tissues and their adjacent normal tissue samples. Combined integrated bioinformatics analysis of mouse and human datasets indicated that 172 genes were consistently deregulated in both human gastric cancer samples and Tff1-KO LGD lesions (P<0...
March 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28277541/the-foxm1-abcc5-axis-contributes-to-paclitaxel-resistance-in-nasopharyngeal-carcinoma-cells
#3
Youxiang Hou, Qianling Zhu, Zheng Li, Yongbo Peng, Xiaohui Yu, Bowen Yuan, Yijun Liu, Youhong Liu, Linglong Yin, Yuchong Peng, Zhenghua Jiang, Jinping Li, Bowen Xie, Yumei Duan, Guolin Tan, Kurban Gulina, Zhicheng Gong, Lunquan Sun, Xuegong Fan, Xiong Li
Paclitaxel is clinically used as a first-line chemotherapeutic regimen for several cancer types, including head and neck cancers. However, acquired drug resistance results in the failure of therapy, metastasis and relapse. The drug efflux mediated by ATP-binding cassette (ABC) transporters and the survival signals activated by forkhead box (FOX) molecules are critical in the development of paclitaxel drug resistance. Whether FOX molecules promote paclitaxel resistance through drug efflux remains unknown. In this study, we developed several types of paclitaxel-resistant (TR) nasopharyngeal carcinoma (NPC) cells...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28276310/basic-transcription-factor-3-is-required-for-proliferation-and-epithelial-mesenchymal-transition-via-regulation-of-foxm1-and-jak2-stat3-signaling-in-gastric-cancer
#4
De-Zhong Zhang, Bing-He Chen, Lan-Fang Zhang, Ming-Kun Cheng, Xiang-Jie Fang, Xin-Jun Wu
Gastric cancer (GC) is the most common epithelial malignancy worldwide. Basic transcription factor 3 (BTF3) plays a crucial role in the regulation of various biological processes. We designed experiments to investigate the molecular mechanism underlying the role of BTF3 in GC cell proliferation and metastasis. We confirmed that BTF3 expression was decreased in GC tissues and several GC cell lines. Lentivirus-mediated downregualtion of BTF3 reduced cell proliferation, induced S and G2/M cell cycle arrest, and increased apoptosis...
March 8, 2017: Oncology Research
https://www.readbyqxmd.com/read/28260073/foxm1-regulates-glycolysis-in-hepatocellular-carcinoma-by-transactivating-glucose-transporter-1-expression
#5
Runze Shang, Meng Pu, Yu Li, Desheng Wang
The Forkhead box M1 (FOXM1) transcription factor plays crucial roles in the initiation and progression of various malignancies, including hepatocellular carcinoma (HCC). However, the mechanism by which FOXM1 regulates cancer metabolism remains unclear. In the present study, overexpression and RNA interference (RNAi) approaches were used to investigate the role of FOXM1 in the regulation of glycolysis in vitro. Luciferase reporter assays were used to explore the transcriptional regulation of the glucose transporter 1 (GLUT1) promoter by FOXM1...
February 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28258481/diarylheptanoids-suppress-proliferation-of-pancreatic-cancer-panc-1-cells-through-modulating-shh-gli-foxm1-pathway
#6
Guang-Zhi Dong, Ji Hye Jeong, Yu-Ih Lee, So Yoon Lee, Hui-Yuan Zhao, Raok Jeon, Hwa Jin Lee, Jae-Ha Ryu
Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1)...
March 3, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28249813/induction-of-chromosome-instability-by-activation-of-yes-associated-protein-and-forkhead-box-m1-in-liver-cancer
#7
Sofia M E Weiler, Federico Pinna, Thomas Wolf, Teresa Lutz, Aman Geldiyev, Carsten Sticht, Maria Knaub, Stefan Thomann, Michaela Bissinger, Shan Wan, Stephanie Rössler, Diana Becker, Norbert Gretz, Hauke Lang, Frank Bergmann, Vladimir Ustiyan, Tatiana V Kalin, Stephan Singer, Ju-Seog Lee, Jens U Marquardt, Peter Schirmacher, Vladimir V Kalinichenko, Kai Breuhahn
BACKGROUND & AIMS: Many different types of cancer cells have chromosome instability. The hippo pathway leads to phosphorylation of the transcriptional activator yes associated protein 1 (YAP1, YAP), which regulates proliferation and has been associated with development of liver cancer. We investigated the effects of hippo signaling via YAP on chromosome stability and hepatocarcinogenesis in humans and mice. METHODS: We analyzed transcriptome data from 242 patients with hepatocellular carcinoma (HCC) to search for gene signatures associated with chromosomal instability; we investigated associations with overall survival time and cancer recurrence using Kaplan-Meier curves...
February 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28225180/microrna-216b-inhibits-cell-proliferation-and-migration-in-human-melanoma-by-targeting-foxm1-in-vitro-and-in-vivo
#8
Mengyao Sun, Xiaopeng Wang, Chen Tu, Shuang Wang, Jianqiang Qu, Shengxiang Xiao
MicroRNAs (miRNAs) play an increasingly important role in cancer growth by coordinately suppressing genes that controlcell migration, proliferationand invasion. The above results can be achieved through the regulation of gene expression by miRNAs bysuppressing translation or the directsequence-specific degradation of the targetedmRNA. In the present study, we indicate that the expression of miR-216b could be effectively repressed both in human melanoma tissues through a comparison with primary melanoma and in human melanoma cell lines through a comparison with a normal human keratinocyte line...
February 22, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28199985/foxm1-promotes-the-progression-of-prostate-cancer-by-regulating-psa-gene-transcription
#9
Youhong Liu, Yijun Liu, Bowen Yuan, Linglong Yin, Yuchong Peng, Xiaohui Yu, Weibing Zhou, Zhicheng Gong, Jianye Liu, Leye He, Xiong Li
Androgen/AR is the primary contributor to prostate cancer (PCa) progression by regulating Prostate Specific Antigen (PSA) gene transcription. The disease inevitably evolves to androgen-independent (AI) status. Other mechanisms by which PSA is regulated and develops to AI have not yet been fully determined. FOXM1 is a cell proliferation-specific transcription factor highly expressed in PCa cells compared to non-malignant prostate epithelial cells, suggesting that the aberrant overexpression of FOXM1 contributes to PCa development...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187446/targeting-of-apoptotic-pathways-by-smac-or-bh3-mimetics-distinctly-sensitizes-paclitaxel-resistant-triple-negative-breast-cancer-cells
#10
Effrosini G Panayotopoulou, Anna-Katharina Müller, Melanie Börries, Hauke Busch, Guohong Hu, Sima Lev
Standard chemotherapy is the only systemic treatment for triple-negative breast cancer (TNBC), and despite the good initial response, resistance remains a major therapeutic obstacle. Here, we employed a High-Throughput Screen to identify targeted therapies that overcome chemoresistance in TNBC. We applied short-term paclitaxel treatment and screened 320 small-molecule inhibitors of known targets to identify drugs that preferentially and efficiently target paclitaxel-treated TNBC cells. Among these compounds the SMAC mimetics (BV6, Birinapant) and BH3-mimetics (ABT-737/263) were recognized as potent targeted therapy for multiple paclitaxel-residual TNBC cell lines...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187428/a-novel-integrative-risk-index-of-papillary-thyroid-cancer-progression-combining-genomic-alterations-and-clinical-factors
#11
Qing Cheng, Xuechan Li, Chaitanya R Acharya, Terry Hyslop, Julie Ann Sosa
Although the majority of papillary thyroid cancer (PTC) is indolent, a subset of PTC behaves aggressively despite the best available treatment. A major clinical challenge is to reliably distinguish early on between those patients who need aggressive treatment from those who do not. Using a large cohort of PTC samples obtained from The Cancer Genome Atlas (TCGA), we analyzed the association between disease progression and multiple forms of genomic data, such as transcriptome, somatic mutations, and somatic copy number alterations, and found that genes related to FOXM1 signaling pathway were significantly associated with PTC progression...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184921/tanshinone%C3%A2-iia-suppresses-gastric-cancer-cell-proliferation-and-migration-by-downregulation-of-foxm1
#12
Jiao Yu, Xiaoxia Wang, Yuhua Li, Bin Tang
Tanshinone IIA (TSN) exhibits a variety of anticancer effects. However, whether it inhibits gastric cancer (GC) cell proliferation and migration and the mechanism remain unclear. In the present study, different concentrations of TSN were co-incubated with SGC-7901 cells. The pcDNA-FOXM1 or FOXM1-siRNA plasmid was transfected into cells before treatment with 5 µg/l TSN. The proliferation and migration abilities of the SGC-7901 cells were tested by MTT and wound healing assays. Western blotting was used to investigate the expression levels of P21, Ki-67, PCNA, MMP-2, MMP-9 and FOXM1...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28176242/roles-of-foxm1-in-cell-regulation-and-breast-cancer-targeting-therapy
#13
REVIEW
Xin Song, Samuel Selorm Fiati Kenston, Jinshun Zhao, Danting Yang, Yuanliang Gu
Forkhead box M1 (FoxM1) is an oncogenic transcription factor involved in a wide variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism and DNA damage response. It is overexpressed in many human cancers, especially in breast cancers. Posttranslational modifications are known to play an important role in regulating the expression and transcriptional activity of FoxM1. In this review, we characterize the posttranslational modifications of FoxM1, summarize modifications of FoxM1 by different kinases, explore the relationship between the different sites of modifications and comprehensively describe how posttranslational modifications to regulate the function of FoxM1 by changing protein stability, nucleus localization and transcriptional activity...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28154085/loss-of-foxm1-promotes-erythropoiesis-through-increased-proliferation-of-erythroid-progenitors
#14
Minyoung Youn, Nan Wang, Corinne LaVasseur, Elena Bibikova, Sharon Kam, Bertil Glader, Kathleen M Sakamoto, Anupama Narla
FOXM1 belongs to the fork head/winged-helix family of transcription factors and regulates a network of proliferation-associated genes. Its abnormal upregulation has been shown to be a key driver of cancer progression and an initiating factor in oncogenesis. FOXM1 is also highly expressed in stem/progenitor cells and inhibits their differentiation, suggesting that FOXM1 plays a role in the maintenance of multipotency. However, the exact molecular mechanisms by which FOXM1 regulates human stem/progenitor cells are still uncharacterized...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28148279/aberrant-activation-of-hedgehog-signaling-promotes-cell-proliferation-via-the-transcriptional-activation-of-forkhead-box-m1-in-colorectal-cancer-cells
#15
DeJie Wang, Guohui Hu, Ying Du, Cheng Zhang, Quqin Lu, Nonghua Lv, Shiwen Luo
BACKGROUND: Recent evidence suggests that the aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas, including colorectal cancer (CRC). Forkhead box M1 (FoxM1) controls the expression of a number of cell cycle regulatory proteins, and FoxM1 expression is elevated in a broad range of human malignancies, which suggests that it plays a crucial role in tumorigenesis. However, the mechanisms underlying FoxM1 expression are not fully understood...
February 2, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28114286/foxm1-recruits-nuclear-aurora-kinase-a-to-participate-in-a-positive-feedback-loop-essential-for-the-self-renewal-of-breast-cancer-stem-cells
#16
N Yang, C Wang, Z Wang, S Zona, S-X Lin, X Wang, M Yan, F-M Zheng, S-S Li, B Xu, L Bella, J-S Yong, E W-F Lam, Q Liu
Substantial evidence suggests that breast cancer initiation, recurrence and drug resistance is supported by breast cancer stem cells (BCSCs). Recently, we reported a novel role of Aurora kinase A (AURKA) in BCSCs, as a transactivating co-factor in the induction of the c-Myc oncoprotein. However, the mode of action and transcriptional network of nuclear AURKA in BCSCs remain unknown. Here, we report that nuclear AURKA can be recruited by Forkhead box subclass M1 (FOXM1) as a co-factor to transactivate FOXM1 target genes in a kinase-independent manner...
January 23, 2017: Oncogene
https://www.readbyqxmd.com/read/28087388/unravelling-the-role-of-fatty-acid-metabolism-in-cancer-through-the-foxo3-foxm1-axis
#17
Paula Saavedra-García, Katie Nichols, Zimam Mahmud, Lavender Yuen-Nam Fan, Eric W-F Lam
Obesity and cachexia represent divergent states of nutritional and metabolic imbalance but both are intimately linked to cancer. There is an extensive overlap in their signalling pathways and molecular components involved such as fatty acids (FAs), which likely play a crucial role in cancer. Forkhead box (FOX) proteins are responsible of a wide range of transcriptional programmes during normal development, and the FOXO3-FOXM1 axis is associated with cancer initiation, progression and drug resistance. Free fatty acids (FFAs), FA synthesis and β-oxidation are associated with cancer development and progression...
January 10, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28078605/transcriptional-regulatory-network-analysis-for-gastric-cancer-based-on-mrna-microarray
#18
Yan Wang
We aimed to screen the differential expressed genes (DEGs) and transcriptional factors (TFs) related to gastric cancer. GSE19826 microarray data downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) and PPI network of DEGs were constructed by the Retrieval of Interacting Genes database. Pathway enrichment analysis of DEGs were performed by Gene Set Enrichment Analysis. Then, the transcriptional regulatory network was constructed based on TRANSFAC database. Finally, regulatory impact factor (RIF) of TF was calculated...
January 11, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28075524/topk-t-lak-cell-originated-protein-kinase-inhibitor-exhibits-growth-suppressive-effect-on-small-cell-lung-cancer
#19
Jae-Hyun Park, Hiroyuki Inoue, Taigo Kato, Makda Zewde, Takashi Miyamoto, Yo Matsuo, Ravi Salgia, Yusuke Nakamura
T-lymphokine-activated killer cell-originated protein kinase (TOPK) plays critical roles in cancer cell proliferation as well as maintenance of cancer stem cells (CSC). Small cell lung cancer (SCLC) has highly aggressive phenotype, reveals early spread to distant sites, and results in dismal prognosis with little effective treatment. In this study, we demonstrate that TOPK expression was highly upregulated in both SCLC cell lines and primary tumors. Similar to siRNA-mediated TOPK knockdown effects, treatment with a potent TOPK inhibitor, OTS514, effectively suppressed growth of SCLC cell lines (IC50 ; 0...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28061449/central-spindle-proteins-and-mitotic-kinesins-are-direct-transcriptional-targets-of-muvb-b-myb-and-foxm1-in-breast-cancer-cell-lines-and-are-potential-targets-for-therapy
#20
Patrick Wolter, Steffen Hanselmann, Grit Pattschull, Eva Schruf, Stefan Gaubatz
The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1...
January 3, 2017: Oncotarget
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