Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia.

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 selectively killed leukemia stem and progenitor cells compared to their normal counterparts and also showed antileukemic activity in mouse models of human leukemia. ShRNA-mediated knockdown of EF-Tu mitochondrial translation factor in leukemic cells reproduced the antileukemia activity of tigecycline. These effects were derivative of mitochondrial biogenesis that, together with an increased basal oxygen consumption, proved to be enhanced in AML versus normal hematopoietic cells and were also important for their difference in tigecycline sensitivity.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Skrtić M,Sriskanthadevan S,Jhas B,Gebbia M,Wang X,Wang Z,Hurren R,Jitkova Y,Gronda M,Maclean N,Lai CK,Eberhard Y,Bartoszko J,Spagnuolo P,Rutledge AC,Datti A,Ketela T,Moffat J,Robinson BH,Cameron JH,Wrana J,Eaves

doi

10.1016/j.ccr.2011.10.015

subject

Has Abstract

pub_date

2011-11-15 00:00:00

pages

674-88

issue

5

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(11)00398-9

journal_volume

20

pub_type

杂志文章
  • The cyclin-like protein Spy1 regulates growth and division characteristics of the CD133+ population in human glioma.

    abstract::The heterogeneity of brain cancers, as most solid tumors, complicates diagnosis and treatment. Identifying and targeting populations of cells driving tumorigenesis is a top priority for the cancer biology field. This is not a trivial task; considerable variance exists in the driving mutations, identifying markers, and...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2013.12.006

    authors: Lubanska D,Market-Velker BA,deCarvalho AC,Mikkelsen T,Fidalgo da Silva E,Porter LA

    更新日期:2014-01-13 00:00:00

  • Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia.

    abstract::Human T cell leukemias can arise from oncogenes activated by specific chromosomal translocations involving the T cell receptor genes. Here we show that five different T cell oncogenes (HOX11, TAL1, LYL1, LMO1, and LMO2) are often aberrantly expressed in the absence of chromosomal abnormalities. Using oligonucleotide m...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/s1535-6108(02)00018-1

    authors: Ferrando AA,Neuberg DS,Staunton J,Loh ML,Huard C,Raimondi SC,Behm FG,Pui CH,Downing JR,Gilliland DG,Lander ES,Golub TR,Look AT

    更新日期:2002-02-01 00:00:00

  • No T without D3: a critical role for cyclin D3 in normal and malignant precursor T cells.

    abstract::A definitive knockout reported in this issue of Cancer Cell by Sicinska et al. reveals an unsuspected role for cyclin D3 in normal T cell development and suggests new therapeutic possibilities in precursor T cell leukemia. ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章,评审

    doi:10.1016/s1535-6108(03)00305-2

    authors: Weng AP,Aster JC

    更新日期:2003-12-01 00:00:00

  • Of Snail, mice, and women.

    abstract::Mechanisms for breast cancer recurrence and metastases are poorly understood. New evidence from a transgenic mouse mammary tumor model suggests that the transcriptional repressor, Snail, may play a role in recurrence by downregulating E-cadherin and inducing an epithelial-to-mesenchymal transition. Preliminary informa...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2005.08.006

    authors: Davidson NE,Sukumar S

    更新日期:2005-09-01 00:00:00

  • The Dual Roles of the Atypical Protein Kinase Cs in Cancer.

    abstract::Atypical protein kinase C (aPKC) isozymes, PKCλ/ι and PKCζ, are now considered fundamental regulators of tumorigenesis. However, the specific separation of functions that determine their different roles in cancer is still being unraveled. Both aPKCs have pleiotropic context-dependent functions that can translate into ...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.ccell.2019.07.010

    authors: Reina-Campos M,Diaz-Meco MT,Moscat J

    更新日期:2019-09-16 00:00:00

  • Singling Out Chromosome Gains in Tumor Evolution.

    abstract::In this issue of Cancer Cell, Sheltzer et al. shed new light on Theodor Boveri's century-old hypothesis by demonstrating that aneuploidy characterized by single-chromosome gains acts to suppress tumorigenesis and that aneuploidy itself is a nidus for genomic instability. ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2017.01.011

    authors: Naylor RM,van Deursen JM

    更新日期:2017-02-13 00:00:00

  • GEMMs shine a light on resistance to androgen deprivation therapy for prostate cancer.

    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

    authors: Karantanos T,Thompson TC

    更新日期:2013-07-08 00:00:00

  • PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress.

    abstract::Cancer cells reprogram their metabolism using different strategies to meet energy and anabolic demands to maintain growth and survival. Understanding the molecular and genetic determinants of these metabolic programs is critical to successfully exploit them for therapy. Here, we report that the oncogenic melanocyte li...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2012.11.020

    authors: Vazquez F,Lim JH,Chim H,Bhalla K,Girnun G,Pierce K,Clish CB,Granter SR,Widlund HR,Spiegelman BM,Puigserver P

    更新日期:2013-03-18 00:00:00

  • Tumor stroma-derived TGF-beta limits myc-driven lymphomagenesis via Suv39h1-dependent senescence.

    abstract::Activated RAS/BRAF oncogenes induce cellular senescence as a tumor-suppressive barrier in early cancer development, at least in part, via an oncogene-evoked DNA damage response (DDR). In contrast, Myc activation-although producing a DDR as well-is known to primarily elicit an apoptotic countermeasure. Using the Emu-my...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2009.12.043

    authors: Reimann M,Lee S,Loddenkemper C,Dörr JR,Tabor V,Aichele P,Stein H,Dörken B,Jenuwein T,Schmitt CA

    更新日期:2010-03-16 00:00:00

  • A TeNaCious foundation for the metastatic niche.

    abstract::In the July issue of Nature Medicine, Massagué and colleagues define a biphasic role for the extracellular matrix protein tenascin C as a metastatic niche component in lung colonization by breast cancer cells. These results provide a rationale for designing therapies targeting metastatic progression by disrupting its ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2011.08.004

    authors: Matei I,Ghajar CM,Lyden D

    更新日期:2011-08-16 00:00:00

  • The ups and downs of SRC regulation: tumor suppression by Cbp.

    abstract::Tight control of the tyrosine kinase activity of c-Src is critical for regulating its oncogenic potential. In a recent issue of Molecular Cell, Oneyama et al. (2008a) report that the membrane-bound adaptor protein Cbp (also known as PAG) can suppress c-Src-mediated cell transformation and tumorigenesis by binding and ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2008.05.011

    authors: Resh MD

    更新日期:2008-06-01 00:00:00

  • Siah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine phenotype and neuroendocrine prostate tumors.

    abstract::Neuroendocrine (NE) phenotype, seen in >30% of prostate adenocarcinomas (PCa), and NE prostate tumors are implicated in aggressive prostate cancer. Formation of NE prostate tumors in the TRAMP mouse model was suppressed in mice lacking the ubiquitin ligase Siah2, which regulates HIF-1alpha availability. Cooperation be...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2010.05.024

    authors: Qi J,Nakayama K,Cardiff RD,Borowsky AD,Kaul K,Williams R,Krajewski S,Mercola D,Carpenter PM,Bowtell D,Ronai ZA

    更新日期:2010-07-13 00:00:00

  • Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations.

    abstract::The SH2-containing tyrosine phosphatase Shp2 (PTPN11) is required for growth factor and cytokine signaling. Germline Shp2 mutations cause Noonan Syndrome (NS), which is associated with increased risk of juvenile myelomonocytic leukemia (JMML). Somatic Shp2 mutations occur in sporadic JMML and other leukemias. We found...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2005.01.010

    authors: Mohi MG,Williams IR,Dearolf CR,Chan G,Kutok JL,Cohen S,Morgan K,Boulton C,Shigematsu H,Keilhack H,Akashi K,Gilliland DG,Neel BG

    更新日期:2005-02-01 00:00:00

  • EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in glioblastoma.

    abstract::EGFRvIII, a frequently occurring mutation in primary glioblastoma, results in a protein product that cannot bind ligand, but signals constitutively. Deducing how EGFRvIII causes transformation has been difficult because of autocrine and paracrine loops triggered by EGFRvIII alone or in heterodimers with wild-type EGFR...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2013.09.004

    authors: Fan QW,Cheng CK,Gustafson WC,Charron E,Zipper P,Wong RA,Chen J,Lau J,Knobbe-Thomsen C,Weller M,Jura N,Reifenberger G,Shokat KM,Weiss WA

    更新日期:2013-10-14 00:00:00

  • Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis.

    abstract::The metastatic process of colorectal cancer (CRC) is not fully understood and effective therapies are lacking. We show that activation of NOTCH1 signaling in the murine intestinal epithelium leads to highly penetrant metastasis (100% metastasis; with >80% liver metastases) in KrasG12D-driven serrated cancer. Transcrip...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2019.08.003

    authors: Jackstadt R,van Hooff SR,Leach JD,Cortes-Lavaud X,Lohuis JO,Ridgway RA,Wouters VM,Roper J,Kendall TJ,Roxburgh CS,Horgan PG,Nixon C,Nourse C,Gunzer M,Clark W,Hedley A,Yilmaz OH,Rashid M,Bailey P,Biankin AV,Campbell

    更新日期:2019-09-16 00:00:00

  • Metastatic colon cancer cells negotiate the intravasation Notch.

    abstract::In this issue of Cancer Cell, Sonoshita et al. report that Aes/Grg5 prevents metastasis of colorectal cancer cells by sequestering and inactivating Notch transcriptional effectors in distinct nuclear foci. Loss of Aes/Grg5 in invasive cancer cells where Notch is activated by stroma-expressed ligands promotes invasion,...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2011.01.003

    authors: Christofori G

    更新日期:2011-01-18 00:00:00

  • ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis.

    abstract::Inhibition of ERK-MAPK signaling by expression of dominant-negative MEK1 in the tumor vasculature suppresses angiogenesis and tumor growth. In an organotypic tissue culture angiogenesis assay, ERK-MAPK inhibition during the migratory phase results in loss of bipolarity, detachment, and cell death of isolated endotheli...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2005.12.021

    authors: Mavria G,Vercoulen Y,Yeo M,Paterson H,Karasarides M,Marais R,Bird D,Marshall CJ

    更新日期:2006-01-01 00:00:00

  • c-Raf in KRas Mutant Cancers: A Moving Target.

    abstract::Therapies for KRas cancers remain a major clinical need. In the current issue of Cancer Cell, Sanclemente and coworkers in Mariano Barbacid's group validate c-Raf as a prime target for these cancers. c-Raf ablation caused regression of advanced KRasG12V/Trp53 tumors, without obvious systemic toxicity and without affec...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2018.01.017

    authors: McCormick F

    更新日期:2018-02-12 00:00:00

  • Targeting the lncRNA SAMMSON Reveals Metabolic Vulnerability in Melanoma.

    abstract::In a recent study, Leucci et al. report a role for the long non-coding RNA SAMMSON in driving mitochondrial function in melanoma. Targeting SAMMSON, the gene of which is frequently co-amplified with MITF, highlights a new cell-type-specific therapeutic vulnerability in melanoma irrespective of BRAF, NRAS, or p53 statu...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2016.04.010

    authors: Goding CR

    更新日期:2016-05-09 00:00:00

  • Elevated CXorf67 Expression in PFA Ependymomas Suppresses DNA Repair and Sensitizes to PARP Inhibitors.

    abstract::Ependymoma is the third most common pediatric tumor with posterior fossa group A (PFA) being its most aggressive subtype. Ependymomas are generally refractory to chemotherapies and thus lack any effective treatment. Here, we report that elevated expression of CXorf67 (chromosome X open reading frame 67), which frequen...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2020.10.009

    authors: Han J,Yu M,Bai Y,Yu J,Jin F,Li C,Zeng R,Peng J,Li A,Song X,Li H,Wu D,Li L

    更新日期:2020-12-14 00:00:00

  • When LMO1 Meets MYCN, Neuroblastoma Is Metastatic.

    abstract::LMO1 is a high-risk neuroblastoma susceptibility gene, but how LMO1 cooperates with MYCN in neuroblastoma tumorigenesis is unclear. In this issue of Cancer Cell, Zhu et al. develop a novel zebrafish model that elucidates a mechanism by which LMO1 and MYCN synergistically initiate neuroblastoma and contribute to metast...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2017.08.014

    authors: Liu Z,Thiele CJ

    更新日期:2017-09-11 00:00:00

  • High-throughput Phenotyping of Lung Cancer Somatic Mutations.

    abstract::Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2016.06.022

    authors: Berger AH,Brooks AN,Wu X,Shrestha Y,Chouinard C,Piccioni F,Bagul M,Kamburov A,Imielinski M,Hogstrom L,Zhu C,Yang X,Pantel S,Sakai R,Watson J,Kaplan N,Campbell JD,Singh S,Root DE,Narayan R,Natoli T,Lahr DL,Tiro

    更新日期:2016-08-08 00:00:00

  • Synergy between PPARgamma ligands and platinum-based drugs in cancer.

    abstract::PPARgamma is a member of the nuclear receptor family for which agonist ligands have antigrowth effects. However, clinical studies using PPARgamma ligands as a monotherapy failed to show a beneficial effect. Here we have studied the effects of PPARgamma activation with chemotherapeutic agents in current use for specifi...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2007.02.025

    authors: Girnun GD,Naseri E,Vafai SB,Qu L,Szwaya JD,Bronson R,Alberta JA,Spiegelman BM

    更新日期:2007-05-01 00:00:00

  • A New Role for Lyn in the CLL Microenvironment.

    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

    authors: Dong S,Byrd JC

    更新日期:2016-10-10 00:00:00

  • Cancer therapeutics in yeast.

    abstract::The budding yeast Saccharomyces cerevisiae is a genetically tractable model system with which to establish the cellular target of a given agent and investigate mechanisms of drug action. ...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/s1535-6108(02)00160-5

    authors: Bjornsti MA

    更新日期:2002-10-01 00:00:00

  • Advancing the field of drug delivery: taking aim at cancer.

    abstract::Drug delivery systems for cancer therapeutics have now been used by millions of patients and have resulted in the creation of new therapies as well as significantly improving existing ones. Here we discuss a number of the drug delivery systems that have been approved by regulatory authorities and that are currently in...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/s1535-6108(03)00276-9

    authors: Moses MA,Brem H,Langer R

    更新日期:2003-11-01 00:00:00

  • A catalytic role for proangiogenic marrow-derived cells in tumor neovascularization.

    abstract::Small numbers of proangiogenic bone marrow-derived cells (BMDCs) can play pivotal roles in tumor progression. In this issue of Cancer Cell, two papers, utilizing different tumor angiogenesis models, both find that activated MMP-9 delivered by BMDCs modulates neovessel remodeling, thereby promoting tumor growth. The ch...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2008.02.016

    authors: Seandel M,Butler J,Lyden D,Rafii S

    更新日期:2008-03-01 00:00:00

  • Deubiquitination and Stabilization of PD-L1 by CSN5.

    abstract::Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2016.10.010

    authors: Lim SO,Li CW,Xia W,Cha JH,Chan LC,Wu Y,Chang SS,Lin WC,Hsu JM,Hsu YH,Kim T,Chang WC,Hsu JL,Yamaguchi H,Ding Q,Wang Y,Yang Y,Chen CH,Sahin AA,Yu D,Hortobagyi GN,Hung MC

    更新日期:2016-12-12 00:00:00

  • A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer.

    abstract::Elucidating the determinants of aggressiveness in lethal prostate cancer may stimulate therapeutic strategies that improve clinical outcomes. We used experimental models and clinical databases to identify GATA2 as a regulator of chemotherapy resistance and tumorigenicity in this context. Mechanistically, direct upregu...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2014.11.013

    authors: Vidal SJ,Rodriguez-Bravo V,Quinn SA,Rodriguez-Barrueco R,Lujambio A,Williams E,Sun X,de la Iglesia-Vicente J,Lee A,Readhead B,Chen X,Galsky M,Esteve B,Petrylak DP,Dudley JT,Rabadan R,Silva JM,Hoshida Y,Lowe SW,Cordo

    更新日期:2015-02-09 00:00:00

  • Lymphotoxins: new targets for hepatocellular carcinoma.

    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

    authors: Villanueva A,Savic R,Llovet JM

    更新日期:2009-10-06 00:00:00