Abstract:
:The dynamic and reversible N6-methyladenosine (m6A) RNA modification installed and erased by N6-methyltransferases and demethylases regulates gene expression and cell fate. We show that the m6A demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs. Integrated transcriptome and m6A-seq analyses revealed altered expression of certain ALKBH5 target genes, including the transcription factor FOXM1. ALKBH5 demethylates FOXM1 nascent transcripts, leading to enhanced FOXM1 expression. Furthermore, a long non-coding RNA antisense to FOXM1 (FOXM1-AS) promotes the interaction of ALKBH5 with FOXM1 nascent transcripts. Depleting ALKBH5 and FOXM1-AS disrupted GSC tumorigenesis through the FOXM1 axis. Our work uncovers a critical function for ALKBH5 and provides insight into critical roles of m6A methylation in glioblastoma.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Zhang S,Zhao BS,Zhou A,Lin K,Zheng S,Lu Z,Chen Y,Sulman EP,Xie K,Bögler O,Majumder S,He C,Huang Sdoi
10.1016/j.ccell.2017.02.013subject
Has Abstractpub_date
2017-04-10 00:00:00pages
591-606.e6issue
4eissn
1535-6108issn
1878-3686pii
S1535-6108(17)30056-9journal_volume
31pub_type
杂志文章相关文献
CANCER CELL文献大全abstract::It was only 3 years ago that an acquired translocation of EML4 with ALK leading to the expression of an EML4-ALK oncoprotein in non-small cell lung cancer (NSCLC) was reported. Tumor cells expressing EML4-ALK are "addicted" to its continued function. Now, crizotinib, an oral ALK inhibitor, is demonstrated to provide d...
journal_title:Cancer cell
pub_type: 杂志文章,评审
doi:10.1016/j.ccr.2010.11.033
更新日期:2010-12-14 00:00:00
abstract::The increased motility and invasiveness of tumor cells are reminiscent of epithelial-mesenchymal transition (EMT), which occurs during embryonic development, wound healing, and metastasis. In this study, we found that Snail is stabilized by the inflammatory cytokine TNFalpha through the activation of the NF-kappaB pat...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2009.03.016
更新日期:2009-05-05 00:00:00
abstract::Emerging strategies in cancer therapeutics link the genomic mutational and proteomic landscape, allowing intelligent reasoning on target selection. In this issue of Cancer Cell, Piccinin and colleagues use this approach to demonstrate that the mesenchymal protein Twist1 inhibits p53, providing a novel target for react...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2012.08.020
更新日期:2012-09-11 00:00:00
abstract::Activating mutations in BRAF are the most common genetic alterations in melanoma. Inhibition of BRAF by small molecules leads to cell-cycle arrest and apoptosis. We show here that BRAF inhibition also induces an oxidative phosphorylation gene program, mitochondrial biogenesis, and the increased expression of the mitoc...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2013.02.003
更新日期:2013-03-18 00:00:00
abstract::Activating mutations in GNAQ/GNA11, encoding Gαq G proteins, are initiating oncogenic events in uveal melanoma (UM). However, there are no effective therapies for UM. Using an integrated bioinformatics pipeline, we found that PTK2, encoding focal adhesion kinase (FAK), represents a candidate synthetic lethal gene with...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2019.01.009
更新日期:2019-03-18 00:00:00
abstract::Mutant RAS-driven tumorigenesis was thought for decades to arise independently of wild-type RAS isoforms, but recent evidence indicates wild-type isoforms are involved. In this issue of Cancer Cell, Grabocka and colleagues report how the loss of wild-type RAS alters oncogenic signaling and dampens the DNA-damage respo...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2014.01.029
更新日期:2014-02-10 00:00:00
abstract::To identify FDA-approved agents targeting leukemic cells, we performed a chemical screen on two human leukemic cell lines and identified the antimicrobial tigecycline. A genome-wide screen in yeast identified mitochondrial translation inhibition as the mechanism of tigecycline-mediated lethality. Tigecycline selective...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2011.10.015
更新日期:2011-11-15 00:00:00
abstract::To metastasize, a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets. We performed a microRNA analysis of human melanoma, a highly invasive c...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2011.05.027
更新日期:2011-07-12 00:00:00
abstract::Adaptive resistance to PI3K-mTOR inhibitors potentially limits the clinical antitumor activities of these agents. In this issue of Cancer Cell, Britschgi and coworkers show that certain tumors acquire resistance to PI3K-mTOR inhibitors through activation of a JAK2-dependent pathway, leading to interleukin-8 secretion....
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2012.11.012
更新日期:2012-12-11 00:00:00
abstract::Unresponsiveness to therapy is a hallmark feature of advanced metastatic melanoma. However, the discovery of BRAF-activating mutations in approximately 50% of human melanomas has provided an attractive therapeutic target. Here, we discuss two recent publications focusing on the mutant BRAF kinase inhibitor PLX4032 tha...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2010.10.001
更新日期:2010-10-19 00:00:00
abstract::It is widely accepted that metastasis is a late event in cancer progression. Here, however, we show that tumor cells can disseminate systemically from earliest epithelial alterations in HER-2 and PyMT transgenic mice and from ductal carcinoma in situ in women. Wild-type mice transplanted with single premalignant HER-2...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2007.12.003
更新日期:2008-01-01 00:00:00
abstract::Obesity is a leading risk factor for cancer. However, understanding the crosstalk between adipocytes and tumor cells in vivo, independently of dietary contributions, is a major gap in the field. Here we used a prostate cancer (PCa) mouse model in which the signaling adaptor p62/Sqstm1 is selectively inactivated in adi...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2018.03.001
更新日期:2018-04-09 00:00:00
abstract::PIK3R1 (p85α regulatory subunit of PI3K) is frequently mutated across cancer lineages. Herein, we demonstrate that the most common recurrent PIK3R1 mutation PIK3R1(R348∗) and a nearby mutation PIK3R1(L370fs), in contrast to wild-type and mutations in other regions of PIK3R1, confers an unexpected sensitivity to MEK an...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2014.08.017
更新日期:2014-10-13 00:00:00
abstract::The nervous system is emerging as a regulator of malignancy. In this issue of Cancer Cell, Hayakawa et al. demonstrate a feedforward signaling loop in which tumor-derived nerve growth factor promotes enteric tumor innervation, and recruited nerves drive cancer growth through acetylcholine-regulated Wnt signaling and s...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccell.2016.12.008
更新日期:2017-01-09 00:00:00
abstract::We used small molecule screening to discover compounds and mechanisms for overcoming E6 oncogene-mediated drug resistance. Using high-throughput screening in isogenic cell lines, we identified compounds that potentiate doxorubicin's lethality in E6-expressing colon cancer cells. Such compounds included quaternary ammo...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2006.01.012
更新日期:2006-02-01 00:00:00
abstract::The protein kinase PKB/Akt has long been associated with regulating signaling pathways that promote cell survival and cell growth, for example, in response to growth factors. In contrast, the DNA-dependent protein kinase (DNA-PK) is required for the repair of DNA damage and for cell survival after exposure to DNA-dama...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2008.04.010
更新日期:2008-05-01 00:00:00
abstract::In this issue of Cancer Cell, Haybaeck et al. unravel the role of lymphotoxin pathway in the development of hepatocellular carcinoma (HCC). Aberrant activation of this cascade in mice livers recapitulates the stages of fibrosis and inflammation that precedes human liver cancer, providing a novel family of potential th...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2009.09.012
更新日期:2009-10-06 00:00:00
abstract::The PI3K signaling axis is frequently activated in cancer resulting from inactivation of its negative regulator PTEN or activating mutations of the p110alpha catalytic subunit of PI3K. In this issue of Cancer Cell, Jaiswal et al. report that mutations in the p85alpha regulatory subunit of PI3K can also activate this p...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2009.11.017
更新日期:2009-12-08 00:00:00
abstract::In this issue of Cancer Cell, Park et al. demonstrate that anti-erbB2 antibody primes adaptive immunity for increased tumor clearance and suggest that chemotherapy may in fact interfere with this process. ...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2010.07.009
更新日期:2010-08-09 00:00:00
abstract::The TFAP2C/AP-2γ transcription factor regulates luminal breast cancer genes, and loss of TFAP2C induces epithelial-mesenchymal transition. By contrast, the highly homologous family member, TFAP2A, lacks transcriptional activity at luminal gene promoters. A detailed structure-function analysis identified that sumoylati...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2014.04.008
更新日期:2014-06-16 00:00:00
abstract::TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic d...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2018.08.003
更新日期:2018-09-10 00:00:00
abstract::Molecular mechanisms associated with tumor metastasis remain poorly understood. Here we report that acquired expression of periostin by colon cancer cells greatly promoted metastatic development of colon tumors. Periostin is overexpressed in more than 80% of human colon cancers examined with highest expression in meta...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/s1535-6108(04)00081-9
更新日期:2004-04-01 00:00:00
abstract::The role of Lyn, both a positive and a negative regulator of B and myeloid cells, in chronic lymphocytic leukemia (CLL) has not been well characterized. In this issue of Cancer Cell, Nguyen et al. demonstrated that Lyn in macrophages rather than in CLL cells is critical for the malignancy. ...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccell.2016.09.018
更新日期:2016-10-10 00:00:00
abstract::Androgen deprivation therapy (ADT) for advanced prostate cancer inexorably leads to resistance, and clinically useful biomarkers are lacking. The value of genetically engineered mice for coclinical studies is clearly demonstrated in a recent publication that reveals XAF1, XIAP, and SRD5A1 as novel predictive biomarker...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2013.06.007
更新日期:2013-07-08 00:00:00
abstract::The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels o...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2016.03.002
更新日期:2016-04-11 00:00:00
abstract::Adoptive T cell immunotherapy is an evolving technology with the potential of providing a means to safely and effectively target tumor cells for destruction. ...
journal_title:Cancer cell
pub_type: 杂志文章,评审
doi:10.1016/s1535-6108(03)00113-2
更新日期:2003-05-01 00:00:00
abstract::Myeloid-derived suppressor cells (MDSCs) play a major role in cancer. MDSC expansion is closely associated with tumor progression, but molecular mechanisms of this expansion remain poorly understood. In this issue of Cancer Cell, Strauss and colleagues describe the roles of the nuclear receptor ROR1C in the regulation...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccell.2015.07.007
更新日期:2015-08-10 00:00:00
abstract::Activating mutations in the FLT3 receptor tyrosine kinase occur in 30% of patients with acute myeloid leukemia. Small molecule FLT3 kinase inhibitors show selective antitumor activity in preclinical models. Clinical studies are underway. ...
journal_title:Cancer cell
pub_type: 杂志文章,评审
doi:10.1016/s1535-6108(02)00080-6
更新日期:2002-06-01 00:00:00
abstract::It is established that p38 MAPK can negatively regulate tumorigenesis, but the mechanism is incompletely understood. A new study in this issue of Cancer Cell shows that p38 MAP kinase plays a selective role in tumor initiation mediated by oxidative stress. ...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2007.01.009
更新日期:2007-02-01 00:00:00
abstract::Neuroblastoma, an embryonal cancer of neural crest origin, shows metastases frequently at diagnosis. In this issue of Cancer Cell, Delloye-Bourgeois and colleagues demonstrate that neuroblastoma cell lines and patient-derived xenografts engraft and adopt a metastatic program in chick embryos. They identify Sema3C as a...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccell.2017.09.012
更新日期:2017-10-09 00:00:00