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FoxM1 AND Cancer

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https://www.readbyqxmd.com/read/28087388/unravelling-the-role-of-fatty-acid-metabolism-in-cancer-through-the-foxo3-foxm1-axis
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28051999/foxm1-evokes-5-fluorouracil-resistance-in-colorectal-cancer-depending-on-abcc10
#5
Tao Xie, Jian Geng, Ye Wang, Liya Wang, Mengxi Huang, Jing Chen, Kai Zhang, Lijun Xue, Xiaobei Liu, Xiaobei Mao, Yanan Chen, Qian Wang, Tingting Dai, Lili Ren, Hongju Yu, Rui Wang, Longbang Chen, Cheng Chen, Xiaoyuan Chu
5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for colorectal cancer (CRC). However, frequently occurred 5-FU resistance poses a great challenge in the clinic. Elucidating the underlying mechanisms and developing effective strategies against 5-FU resistance are highly desired. Here we identified the upregulation of FOXM1 in 5-FU nonresponsive CRC patients by gene expression profile analysis and 5-FU-resistant CRC cells by qRT-PCR assay. Silencing of FOXM1 promoted the sensitivity of CRC cells to 5-FU by enhancing cell apoptosis, while overexpression of FOXM1 conferred CRC cells with 5-FU resistance both in vitro and in vivo...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28012972/a-novel-peptide-9r-p201-strongly-inhibits-the-viability-proliferation-and-migration-of-liver-cancer-hepg2-cells-and-induces-apoptosis-by-down-regulation-of-foxm1-expression
#6
Zhenfei Bi, Wenrong Liu, Ruofang Ding, Yiran Wu, Rongkun Dou, Wenwen Zhang, Xue Yuan, Xinrong Liu, Lili Xiong, Zhiyun Guo, Canquan Mao
Overexpression of FoxM1 was closely related to the proliferation, metastasis, chemo-resistance and poor prognosis of various cancers. FoxM1 was regarded as the Achilles' heel of cancer and a potential target for anti-cancer drug discovery. We previously obtained several high affinity peptides from the phage random library against the DNA binding domain of FoxM1c (FoxM1c-DBD) protein. Here in this paper, we found that 9R-P201, one of the novel peptides, showed stronger inhibition to HepG2 cancer cells than those of DU145, HUVEC and L-02 cells with an IC50 of 43...
December 21, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27923917/metadherin-astrocyte-elevated-gene-1-positively-regulates-the-stability-and-function-of-forkhead-box-m1-during-tumorigenesis
#7
Lixuan Yang, Kejun He, Sheng Yan, Yibing Yang, Xinya Gao, Maolei Zhang, Zhibo Xia, Zhengsong Huang, Suyun Huang, Nu Zhang
BACKGROUND: Forkhead box M1 (FOXM1) is overexpressed and activates numerous oncoproteins in tumors. However, the mechanism by which the FOXM1 protein aberrantly accumulates in human cancer remains uncertain. This study was designed to clarify the upstream signaling pathway(s) that regulate FOXM1 protein stability and transcriptional activity. METHODS: Mass spectrometry and immunoprecipitation were performed to identify the FOXM-metadherin (MTDH) interaction. In vivo and in vitro ubiquitination assays were conducted to test the effect of MTDH on FOXM1 stability...
December 6, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27863397/targeting-gli-by-gant61-involves-mechanisms-dependent-on-inhibition-of-both-transcription-and-dna-licensing
#8
Ruowen Zhang, Jiahui Wu, Sylvain Ferrandon, Katie J Glowacki, Janet A Houghton
The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863385/gli1-promotes-colorectal-cancer-metastasis-in-a-foxm1-dependent-manner-by-activating-emt-and-pi3k-akt-signaling
#9
Chuan Zhang, Yong Wang, YiFei Feng, Yue Zhang, Bing Ji, Sen Wang, Ye Sun, Chunyan Zhu, Dongsheng Zhang, Yueming Sun
Colorectal cancer(CRC) is one of the most commonly diagnosed cancers in human beings and metastasis is the main death reason. Recently, Gli1 has been reported to be a key regulator of various cancer biologies and genes expressions. However, the detailed molecular mechanism of Gli1 in CRC metastasis remains largely unknown. In this study, we aimed to investigate the role of Gli1 in CRC metastasis. We used qRT-PCR, Immunohistochemistry and Western blot to test the expression levels of Gli1, Foxm1 and other target genes in the tissues and cells; Lentivirus stable transfection to change the expression levels of Gli1 and Foxm1; Wound-healing, cell invasion, migration assays and tail vein metastatic assay to test the role of Gli1 in CRC metastasis in vitro and vivo...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27756785/a-positive-feedback-loop-of-lncrna-pvt1-and-foxm1-facilitates-gastric-cancer-growth-and-invasion
#10
Xiang Du, Mi-Die Xu, Yiqin Wang, Wei-Wei Weng, Ping Wei, Peng Qi, Qiongyan Zhang, Cong Tan, Shujuan Ni, Lei Dong, Yusi Yang, Wanrun Lin, Qinghua Xu, Dan Huang, Zhaohui Huang, Yuqing Ma, Wei Zhang, Weiqi Sheng
PURPOSE: The long noncoding RNA (lncRNA) PVT1 is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of PVT1 in gastric cancer (GC) tumorigenesis and progression. EXPERIMENTAL DESIGN: The expression level of PVT1 was determined by RT-qPCR analysis in 190 pairs of GC tissues and adjacent normal gastric mucosa tissues (ANTs). The biological functions of PVT1 were assessed by in vitro and in vivo functional experiments...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27716361/long-non-coding-rna-h19-regulates-foxm1-expression-by-competitively-binding-endogenous-mir-342-3p-in-gallbladder-cancer
#11
Shou-Hua Wang, Fei Ma, Zhao-Hui Tang, Xiao-Cai Wu, Qiang Cai, Ming-Di Zhang, Ming-Zhe Weng, Di Zhou, Jian-Dong Wang, Zhi-Wei Quan
BACKGROUND: Long non-coding RNA (lncRNA) H19 has been reported to involve in many kinds of human cancers and functions as an oncogene. Our previous study found that H19 was over-expressed in gallbladder cancer (GBC) and was shown to promote tumor development in GBC. However, the competing endogenous RNA (ceRNA) regulatory network involving H19 in GBC progression has not been fully elucidated. We aim to detect the role of H19 as a ceRNA in GBC. METHODS AND RESULTS: In this study, the expression of H19 and miR-342-3p were analyzed in 35 GBC tissues and matched normal tissues by using quantitative polymerase chain reaction (qRT-PCR)...
October 3, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27698840/association-between-foxm1-and-hedgehog-signaling-pathway-in-human-cervical-carcinoma-by-tissue-microarray-analysis
#12
Hong Chen, Jingjing Wang, Hong Yang, Dan Chen, Panpan Li
Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the formation and development of human tumors, including cervical cancer. Previous studies have indicated that FOXM1 may be a downstream target gene of the Hh signaling pathway, but their association in cervical cancer is largely unknown. In the present study, the expression of FOXM1 and Hh signaling molecules was evaluated by immunohistochemical analysis in a tissue microarray that contained 70 cervical cancer tissues and 10 normal cervical tissues...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27698811/expression-of-foxm1-and-the-emt-associated-protein-e-cadherin-in-gastric-cancer-and-its-clinical-significance
#13
Jing Zhang, Xiao-Yu Chen, Ke-Jian Huang, Wei-Dong Wu, Tao Jiang, Jun Cao, Li-Sheng Zhou, Zheng-Jun Qiu, Chen Huang
The aim of the present study was to investigate the expression of forkhead box M1 (FoxM1) and E-cadherin in tissues of gastric cancer in order to reveal any correlation between FoxM1, E-cadherin and clinicopathological parameters. The association between FoxM1 and E-cadherin in the development and progression of gastric cancer was also investigated. The expression of FoxM1 and E-cadherin in gastric cancer and adjacent normal tissue on tissue microarray was detected using immunohistochemistry. The clinicopathological significance of FoxM1 and E-cadherin in gastric cancer was explored, and the association between FoxM1 and E-cadherin was further examined using statistical techniques...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27698803/expression-and-potential-correlation-among-forkhead-box-protein-m1-caveolin-1-and-e-cadherin-in-colorectal-cancer
#14
Jing Zhang, Kundong Zhang, Lisheng Zhou, Weidong Wu, Tao Jiang, Jun Cao, Kejian Huang, Zhengjun Qiu, Chen Huang
The aim of the present study was to investigate the expression and functions of Forkhead box protein M1 (FoxM1), Caveolin-1 (Cav-1) and E-cadherin in colorectal cancer (CRC), and to determine the correlations among these proteins in CRC development and progression. The protein expression of FoxM1, Cav-1 and E-cadherin was identified using a human CRC and normal tissue microarray. A standard immunohistochemistry assay was performed employing anti-FoxM1, anti-Cav-1 and anti-E-cadherin antibodies. The clinicopathological significance of FoxM1, Cav-1 and E-cadherin in CRC was determined, and correlations were investigated between FoxM1 and Cav-1, FoxM1 and E-cadherin, Cav-1 and E-cadherin, respectively...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27693640/melk-is-an-oncogenic-kinase-essential-for-early-hepatocellular-carcinoma-recurrence
#15
Hongping Xia, Shik Nie Kong, Jianxiang Chen, Ming Shi, Karthik Sekar, Veerabrahma Pratap Seshachalam, Muthukumar Rajasekaran, Brian Kim Poh Goh, London Lucien Ooi, Kam M Hui
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Many kinases have been found to be intimately involved in oncogenesis and the deregulation of kinase function has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. Previously, we have performed gene expression profile analysis on HCC samples and have identified a host of kinases that are remarkably overexpressed in HCC. Among these, the Maternal Embryonic Leucine Zipper Kinase (MELK) is highly overexpressed in HCC and its overexpression strongly correlates with early recurrence and poor patients' survival...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27593933/dlx1-acts-as-a-crucial-target-of-foxm1-to-promote-ovarian-cancer-aggressiveness-by-enhancing-tgf-%C3%AE-smad4-signaling
#16
D W Chan, W W Y Hui, J J Wang, M M H Yung, L M N Hui, Y Qin, R R Liang, T H Y Leung, D Xu, K K L Chan, K-M Yao, B K Tsang, H Y S Ngan
Recent evidence from a comprehensive genome analysis and functional studies have revealed that FOXM1 is a crucial metastatic regulator that drives cancer progression. However, the regulatory mechanism by which FOXM1 exerts its metastatic functions in cancer cells remains obscure. Here, we report that DLX1 acts as a FOXM1 downstream target, exerting pro-metastatic function in ovarian cancers. Both FOXM1 isoforms (FOXM1B or FOXM1C) could transcriptionally upregulate DLX1 through two conserved binding sites, located at +61 to +69bp downstream (TFBS1) and -675 to -667bp upstream (TFBS2) of the DLX1 promoter, respectively...
September 5, 2016: Oncogene
https://www.readbyqxmd.com/read/27563818/cadherin-6-type-2-k-cadherin-cdh6-is-regulated-by-mutant-p53-in-the-fallopian-tube-but-is-not-expressed-in-the-ovarian-surface
#17
Subbulakshmi Karthikeyan, Daniel D Lantvit, Dam Hee Chae, Joanna E Burdette
High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy and may arise in either the fallopian tube epithelium (FTE) or ovarian surface epithelium (OSE). A mutation in p53 is reported in 96% of HGSOC, most frequently at R273 and R248. The goal of this study was to identify specific gene targets in the FTE that are altered by mutant p53, but not in the OSE. Gene analysis revealed that both R273 and R248 mutant p53 reduces CDH6 expression in the oviduct, but CDH6 was not detected in murine OSE cells...
August 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27528030/integrative-analysis-of-mirna-and-gene-expression-reveals-regulatory-networks-in-tamoxifen-resistant-breast-cancer
#18
Tejal Joshi, Daniel Elias, Jan Stenvang, Carla L Alves, Fei Teng, Maria B Lyng, Anne E Lykkesfeldt, Nils Brünner, Jun Wang, Ramneek Gupta, Christopher T Workman, Henrik J Ditzel
Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer, however, tamoxifen resistance is frequently observed. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of miRNA-mediated gene regulation in three clinically-relevant tamoxifen-resistant breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs...
August 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27526106/rnf168-cooperates-with-rnf8-to-mediate-foxm1-ubiquitination-and-degradation-in-breast-cancer-epirubicin-treatment
#19
M Kongsema, S Zona, U Karunarathna, E Cabrera, E P S Man, S Yao, A Shibakawa, U-S Khoo, R H Medema, R Freire, E W-F Lam
The forkhead box M1 (FOXM1) transcription factor has a central role in genotoxic agent response in breast cancer. FOXM1 is regulated at the post-translational level upon DNA damage, but the key mechanism involved remained enigmatic. RNF168 is a ubiquitination E3-ligase involved in DNA damage response. Western blot and gene promoter-reporter analyses showed that the expression level and transcriptional activity of FOXM1 reduced upon RNF168 overexpression and increased with RNF168 depletion by siRNA, suggesting that RNF168 negatively regulates FOXM1 expression...
2016: Oncogenesis
https://www.readbyqxmd.com/read/27521795/foxm1-inhibition-enhances-chemosensitivity-of-docetaxel-resistant-a549-cells-to-docetaxel-via-activation-of-jnk-mitochondrial-pathway
#20
Ke Wang, Xue Zhu, Kai Zhang, Ling Zhu, Fanfan Zhou
Docetaxel is recommended as a second-line chemotherapy agent for the non-small-cell lung cancer (NSCLC); however, drug resistance greatly limits its efficiency. Forkhead box M1 (FoxM1), an oncogenic transcription factor, is believed to be involved in the chemoresistance of various human cancers; whereas the association of FoxM1 with acquired docetaxel-resistance in NSCLC remains unclear. In the present study, we investigated the involvement of FoxM1 in the docetaxel-resistant human lung adenocarcinoma A549 cells (A549/DTX)...
September 2016: Acta Biochimica et Biophysica Sinica
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