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FoxM1 AND Cancer

Xiaodong Jiao, Wenlong Yu, Jianxin Qian, Ying Chen, Peilian Wei, Wenzheng Fang, Guanzhen Yu
BACKGROUND: A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. METHODS: mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples...
May 18, 2018: BMC Cancer
Satoshi Ogura, Yuichi Yoshida, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Hidetoshi Eguchi, Hisakazu Ogita, Yuichiro Doki, Masaki Mori, Tomohide Tatsumi, Tetsuo Takehara
Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of cholesterol biosynthesis in HCC. Inhibition of the mevalonate pathway by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), resulted in reduced expression of FoxM1 and increased cell death in human hepatoma cells...
April 20, 2018: Oncotarget
Bowen Yuan, Youhong Liu, Xiaohui Yu, Linglong Yin, Yuchong Peng, Yingxue Gao, Qianling Zhu, Tuoyu Cao, Yinke Yang, Xuegong Fan, Xiong Li
Therapy-induced expansion of cancer stem cells (CSCs) has been identified as one of the most critical factors contributing to therapeutic resistance, but the mechanisms of this adaptation are not fully understood. UHRF1 is a key epigenetic regulator responsible for therapeutic resistance, and controls the self-renewal of stem cells. In the present study, taxane-resistant cancer cells were established and stem-like cancer cells were expanded. UHRF1 was overexpressed in the taxane-resistant cancer cells, which maintained CSC characteristics...
May 11, 2018: Cell Death & Disease
Recep Bayraktar, Cristina Ivan, Emine Bayraktar, Pinar Kanlikilicer, Nashwa Kabil, Nermin Kahraman, Hamada Ahmed Mokhlis, Didem Karakas, Cristian Rodriguez-Aguayo, Ahmet Arslan, Jianting Sheng, Stephen Tc Wong, Gabriel Lopez-Berestein, George A Calin, Bulent Ozpolat
Purpose - Recent studies indicated that dysregulation of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) is involved in pathogenesis of various human cancers. However, the molecular mechanisms underlying miR-34a are not fully understood in triple-negative breast cancer (TNBC). Experimental Design- We performed  in vitro  functional assays on TNBC cell lines to investigate the role of miR-34a in FOXM1/eEF2K signaling axis. TNBC tumor xenograft models were used for in vivo therapeutic delivery of miR-34a...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Mingzhi Han, Ran Xu, Shuai Wang, Ning Yang, Shilei Ni, Qing Zhang, Yangyang Xu, Xin Zhang, Chao Zhang, Yuzhen Wei, Jianxiong Ji, Bin Huang, Di Zhang, Anjing Chen, Wenjie Li, Rolf Bjerkvig, Xingang Li, Jian Wang
Recent evidence suggests that dysregulation of iron regulatory factors may play essential roles in cancer pathophysiology. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a metalloreductase, which is vital for cellular iron uptake and homeostasis. However, the clinical significance and function of STEAP3 in the development of human gliomas remain unclear. Through analysis of publicly available databases, we found that STEAP3 was highly expressed in malignant gliomas, especially in the mesenchymal glioma molecular subtype and isocitrate dehydrogenase 1/2 (IDH1/2) wild-type gliomas...
May 3, 2018: Neoplasia: An International Journal for Oncology Research
Jae Hee Lee, Hyo-Jung Lee, Deok Yong Sim, Ji Hoon Jung, Ka Ram Kim, Sung-Hoon Kim
Though lambertianic acid (LA) was known to exert antitumor effect in liver and prostate cancers, its underlying anticancer mechanism is never reported in breast cancers so far. Thus, in this study, apoptotic mechanism of LA was elucidated in MDA-MB-231 breast cancer cells. Here, LA increased cytotoxicity in MCF-7 and MDA-MB-231 cells; enhanced sub-G1 population, G2/M arrest, and cleaved poly(ADP-ribose) polymerase; activated phosphorylation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase pathway; and also suppressed phosphorylation of AKT and the expression of forkhead box M1 (FOXM1), X-linked inhibitor of apoptosis protein, B-cell lymphoma 2, and CyclinB1 in MDA-MB-231 cells...
May 2, 2018: Phytotherapy Research: PTR
Pei Cai, Zuoqi Xiao, Tao Pan, Xiaoke Wen, Jianguo Cao, Bo Ouyang
Cancer stem cells (CSCs) are a subset of cancer cells which have self-renewal ability and exist in various tumors. Inhibition of CSCs self-renewal is considered as a new method for tumor therapy. A novel semi-synthetic taxane analogue, Lx2-32c, could overcome drug resistance in various cancer cell lines. In this study, it was found that Lx2-32c inhibited the proliferation and mammosphere formation of MDA-MB-231-derived cancer stem cell-like cells (MCSCLCs) and induced apoptosis, as well as down-regulated the expression of FoxM1 and CD44 in MCSCLCs...
April 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Abdul Khalid Siraj, Poyil Pratheeshkumar, Sandeep Kumar Parvathareddy, Zeeshan Qadri, Saravanan Thangavel, Saeeda Ahmed, Fouad Al-Dayel, Asma Tulbah, Dahish Ajarim, Khawla S Al-Kuraya
Breast cancer (BC) is the most common cause of cancer-related death in females in Saudi Arabia. BC in Saudi women tend to behave more aggressively than breast cancer in the West. Therefore, identification of new molecular targets and treatment strategies are highly warranted to improve patient outcome. FoxM1 has been shown to play a critical role in pathogenesis of various malignancies. In this study, we explored the prevalence and clinical implication of FoxM1 overexpression in Saudi breast cancer. FoxM1 protein overexpression was seen in 79% (770/975) of BC tissues and was associated with aggressive clinical parameters such as younger age (< 30 yrs) ( p = 0...
April 3, 2018: Oncotarget
Na Chai, Hua-Hong Xie, Ji-Peng Yin, Ke-di Sa, Yi Guo, Meng Wang, Jun Liu, Xiao-Fang Zhang, Xiang Zhang, Hong Yin, Yong-Zhan Nie, Kai-Chun Wu, An-Gang Yang, Rui Zhang
The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels...
April 26, 2018: Biochemical and Biophysical Research Communications
Guanghong Xiu, Xiujie Sui, Yirong Wang, Ze Zhang
Forkhead box protein M1 (FOXM1), an important regulator of tumorigenesis in various human tumors, has recently been reported to play a role in the modulation of radiosensitivity in glioma and breast cancer cells. The present study aimed to investigate the effects of FOXM1 on radiotherapy resistance in human lung cancer and to explore the related molecular mechanisms. The results revealed that FOXM1 expression was upregulated in A549 and H1299 cells after IR (Ionizing radiation). FOXM1 inhibition impeded survival fractions, impeded proliferation, and triggered apoptosis after IR...
April 25, 2018: European Journal of Pharmacology
Jiayu Liang, Zhihong Liu, Zijun Zou, Yongquan Tang, Chuan Zhou, Jian Yang, Xin Wei, Yiping Lu
Both epithelial-mesenchymal transition (EMT) and immune regulation are important biological process in malignant tumours. The current research aims to comprehensively explore the potential association between the epithelial-mesenchymal transition (EMT) signature and immune checkpoint signature and its role in predicting the prognosis of clear-cell renal cell carcinoma (ccRCC) patients. EMT-related genes were collected from an experiment-based study and then were investigated using data from the Cancer Genome Atlas...
April 26, 2018: Scientific Reports
Enrique Rozengurt, James Sinnett-Smith, Guido Eibl
Pancreatic ductal adenocarcinoma (PDAC) is generally a fatal disease with no efficacious treatment modalities. Elucidation of signaling mechanisms that will lead to the identification of novel targets for therapy and chemoprevention is urgently needed. Here, we review the role of Yes-associated protein (YAP) and WW-domain-containing Transcriptional co-Activator with a PDZ-binding motif (TAZ) in the development of PDAC. These oncogenic proteins are at the center of a signaling network that involves multiple upstream signals and downstream YAP-regulated genes...
2018: Signal Transduction and Targeted Therapy
Pedro Nicolau-Neto, Antonio Palumbo, Marco De Martino, Francesco Esposito, Tatiana de Almeida Simão, Alfredo Fusco, Luiz Eurico Nasciutti, Nathalia Meireles Da Costa, Luis Felipe Ribeiro Pinto
FOXM1 (forkhead box protein M1) is a transcription factor that participates in all stages of tumor development, mainly through the control of cell cycle and proliferation, regulating the expression of genes involved in G1/S and G2/M transition and M phase progression. The ubiquitin conjugating enzyme E2 (UBE2C) is a member of the anaphase promoting complex/cyclosome, promoting the degradation of several target proteins along cell cycle progression, during metaphase/anaphase transition. FOXM1 and UBE2C have been found overexpressed in a wide range of different solid tumors...
March 29, 2018: Genes
Huafeng Pan, Yudi Zhu, Wei Wei, Siliang Shao, Xin Rui
BACKGROUND: Prostate cancer is a common malignancy and the second leading cause of cancer death in men. Elevated expression of the transcription factor FoxM1 and c-Myc has been identified in prostate cancer. However, the potential mechanism of elevated FoxM1 and c-Myc to the development of prostate cancer has not been identified. METHODS: In this report, the mRNA level of FoxM1 and c-Myc was detected in 30 prostate cancer and para-cancer tissues. Then, we detected the expression level of FoxM1 by real-time PCR and Western blot after disturbance of the expression level of c-Myc in PC-3 cells...
March 20, 2018: World Journal of Surgical Oncology
Fan Yang, Qingjian Wu, Yan Zhang, Haojun Xiong, Xinzhe Li, Bo Li, Wei Xie, Le Zhang, Min Xu, Kebin Zhang, Fengtian He
Renal cell carcinoma (RCC) is the most common kidney malignancy with poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been demonstrated as important regulators in multiple cancers including RCC. LOC653786 is a lncRNA, but its role in cancer remains unclear. In this study, we for the first time found that LOC653786 was upregulated in RCC tissues and cell lines, and this lncRNA promoted growth and cell cycle progression of RCC cells. Moreover, we showed that LOC653786 elevated the expression of forkhead box M1 (FOXM1) and its downstream target genes cyclin D1 and cyclin B1 in RCC cells...
February 23, 2018: Oncotarget
Liang Song, Xiaohang Wang, Zhen Feng
Esophageal squamous cell carcinoma (ESCC) is one of the most common types of malignancies globally. Forkhead box M1 (FOXM1) has important functions in cancer progression. However, the function of FOXM1 signaling in ESCC remains unknown. The aim of the present study was to evaluate the expression level and function of FOXM1 in human ESCC. The present study first detected the FOXM1 expression level in 78 cases of primary ESCC tissues and matched normal tissue samples by immunohistochemistry, western blot analysis and reverse transcription-quantitative polymerase chain reaction...
April 2018: Oncology Letters
Pingping Fang, Jill A Madden, Lisa Neums, K Ryan Moulder, M Laird Forrest, Jeremy Chien
FOXM1 transcription factor network is activated in over 84% of cases in high-grade serous ovarian cancer (HGSOC), and FOXM1 upregulates the expression of genes involved in the homologous recombination (HR) DNA damage and repair (DDR) pathway. However, the role of FOXM1 in poly (ADP-ribose) polymerase (PARP) inhibitor response has not yet been studied. The present study demonstrates that PARP inhibitor (PARPi), olaparib, induces the expression and nuclear localization of FOXM1. Based on ChIP-qPCR, olaparib enhances the binding of FOXM1 to genes involved in HR repair...
March 15, 2018: Molecular Cancer Research: MCR
Xinping Yang, Yuanyuan Shi, Jingzhe Yan, Haitao Fan
The FoxM1 (Forkhead Box M1) transcription factor plays a key role in regulation of cell growth, cell cycle, and transformation. Higher expression of FoxM1 has been observed in various types of human cancers including bladder cancer. However, the exact function of FoxM1 in bladder cancer has not been elucidated. To investigate the cellular and molecular function of FoxM1 in bladder cancer, we measured the consequences of downregulation and upregulation of FoxM1 in bladder cancer cells using MTT assay, wound healing assay, and invasion assay...
2018: American Journal of Translational Research
Syrine Abdeljaoued, Lhem Bettaieb, Meher Nasri, Olfa Adouni, Aida Goucha, Hatem Bouzaiene, Hamouda Boussen, Khaled Rahal, Amor Gamoudi
BACKGROUND: Male breast cancer (MBC) is a rare and neglected disease. Prognostic and predictive factors in MBC are extrapoled from trials conducted on its female counterpart. OBJECTIVE: Since the relationship between the transcription factor Forkhead box M1 (FOXM1) expression and the clinical response to chemotherapy and hormonotherapy in MBC remains unknown, we sought to investigate the predictive value of FOXM1 in MBC. METHODS: FOXM1 expression was assessed in 130 MBC cases...
2018: Breast Disease
Tingyu Wu, Guanghui Wang, Wei Chen, Zhehui Zhu, Yun Liu, Zhenyu Huang, Yuji Huang, Peng Du, Yili Yang, Chen-Ying Liu, Long Cui
The bromodomain and extra-terminal domain inhibitors (BETi) are promising epigenetic drugs for the treatment of various cancers through suppression of oncogenic transcription factors. However, only a subset of colorectal cancer (CRC) cells response to BETi. We investigate additional agents that could be combined with BETi to overcome this obstacle. JQ1-resistant CRC cells were used for screening of the effective combination therapies with JQ1. RNA-seq was performed to explore the mechanism of synergistic effect...
February 22, 2018: Cell Death & Disease
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