Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors.

Abstract:

:In mice, Lkb1 deletion and activation of Kras(G12D) results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Carretero J,Shimamura T,Rikova K,Jackson AL,Wilkerson MD,Borgman CL,Buttarazzi MS,Sanofsky BA,McNamara KL,Brandstetter KA,Walton ZE,Gu TL,Silva JC,Crosby K,Shapiro GI,Maira SM,Ji H,Castrillon DH,Kim CF,García-Echeve

doi

10.1016/j.ccr.2010.04.026

subject

Has Abstract

pub_date

2010-06-15 00:00:00

pages

547-59

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(10)00199-6

journal_volume

17

pub_type

杂志文章
  • Her 2 in 1.

    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

    authors: Smyth MJ,Stagg J

    更新日期:2010-08-09 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

  • Dysfunction of the Reciprocal Feedback Loop between GATA3- and ZEB2-Nucleated Repression Programs Contributes to Breast Cancer Metastasis.

    abstract::How loss-of-function of GATA3 contributes to the development of breast cancer is poorly understood. Here, we report that GATA3 nucleates a transcription repression program composed of G9A and MTA3-, but not MTA1- or MTA2-, constituted NuRD complex. Genome-wide analysis of the GATA3/G9A/NuRD(MTA3) targets identified a ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2015.04.011

    authors: Si W,Huang W,Zheng Y,Yang Y,Liu X,Shan L,Zhou X,Wang Y,Su D,Gao J,Yan R,Han X,Li W,He L,Shi L,Xuan C,Liang J,Sun L,Wang Y,Shang Y

    更新日期:2015-06-08 00:00:00

  • Cell signaling and cancer.

    abstract::During the course of tumor progression, cancer cells acquire a number of characteristic alterations. These include the capacities to proliferate independently of exogenous growth-promoting or growth-inhibitory signals, to invade surrounding tissues and metastasize to distant sites, to elicit an angiogenic response, an...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/s1535-6108(03)00216-2

    authors: Martin GS

    更新日期:2003-09-01 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

  • Proteogenomic Characterization of Human Early-Onset Gastric Cancer.

    abstract::We report proteogenomic analysis of diffuse gastric cancers (GCs) in young populations. Phosphoproteome data elucidated signaling pathways associated with somatic mutations based on mutation-phosphorylation correlations. Moreover, correlations between mRNA and protein abundances provided potential oncogenes and tumor ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2018.12.003

    authors: Mun DG,Bhin J,Kim S,Kim H,Jung JH,Jung Y,Jang YE,Park JM,Kim H,Jung Y,Lee H,Bae J,Back S,Kim SJ,Kim J,Park H,Li H,Hwang KB,Park YS,Yook JH,Kim BS,Kwon SY,Ryu SW,Park DY,Jeon TY,Kim DH,Lee JH,Han SU,

    更新日期:2019-01-14 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

  • Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma.

    abstract::Obesity increases hepatocellular carcinoma (HCC) risks via unknown mediators. We report that hepatic unconventional prefoldin RPB5 interactor (URI) couples nutrient surpluses to inflammation and non-alcoholic steatohepatitis (NASH), a common cause of HCC. URI-induced DNA damage in hepatocytes triggers inflammation via...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2016.05.020

    authors: Gomes AL,Teijeiro A,Burén S,Tummala KS,Yilmaz M,Waisman A,Theurillat JP,Perna C,Djouder N

    更新日期:2016-07-11 00:00:00

  • Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis.

    abstract::Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitant...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2009.01.027

    authors: Pàez-Ribes M,Allen E,Hudock J,Takeda T,Okuyama H,Viñals F,Inoue M,Bergers G,Hanahan D,Casanovas O

    更新日期:2009-03-03 00:00:00

  • Genomic and Transcriptomic Analysis Reveals Incremental Disruption of Key Signaling Pathways during Melanoma Evolution.

    abstract::We elucidated genomic and transcriptomic changes that accompany the evolution of melanoma from pre-malignant lesions by sequencing DNA and RNA from primary melanomas and their adjacent precursors, as well as matched primary tumors and regional metastases. In total, we analyzed 230 histopathologically distinct areas of...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2018.06.005

    authors: Shain AH,Joseph NM,Yu R,Benhamida J,Liu S,Prow T,Ruben B,North J,Pincus L,Yeh I,Judson R,Bastian BC

    更新日期:2018-07-09 00:00:00

  • Turning on a dimer: new insights into MLL chimeras.

    abstract::In this issue of Cancer Cell, demonstrate a novel mechanism for the oncogenic activity of MLL chimeric proteins. By providing coiled-coil or other dimerization domains, the cytoplasmic partners of MLL fusion proteins donate a platform for MLL homodimerization, allowing recruitment of accessory factors needed to activa...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/s1535-6108(03)00192-2

    authors: Hsu K,Look AT

    更新日期:2003-08-01 00:00:00

  • Normal Somatic Mutations in Cancer Transformation.

    abstract::Gene alterations play a prominent role in driving cancer initiation and progression. However, the genetic events that occur in normal cells prior to tumorigenesis are still unknown. Recent studies have started to map somatic mutations in normal human tissues, and here we discuss their implications for our understandin...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2020.11.002

    authors: Wijewardhane N,Dressler L,Ciccarelli FD

    更新日期:2020-11-17 00:00:00

  • In Search of a Cure for Proteostasis-Addicted Cancer: A AAA Target Revealed.

    abstract::Tumorigenesis is often associated with an unbalanced protein homeostasis (proteostasis) network, which sensitizes cancer cells to drugs targeting protein quality control (PQC) regulators. In this issue of Cancer Cell, Anderson and colleagues investigated the anti-cancer activity of a new class of inhibitor against a m...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2015.10.006

    authors: Xia D,Ye Y

    更新日期:2015-11-09 00:00:00

  • Optimal gene expression analysis by microarrays.

    abstract::DNA microarrays make possible the rapid and comprehensive assessment of the transcriptional activity of a cell, and as such have proven valuable in assessing the molecular contributors to biological processes and in the classification of human cancers. The major challenge in using this technology is the analysis of it...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/s1535-6108(02)00181-2

    authors: Miller LD,Long PM,Wong L,Mukherjee S,McShane LM,Liu ET

    更新日期:2002-11-01 00:00:00

  • EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation.

    abstract::The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B cells and targeted by somatic mutations in B cell lymphomas. Here, we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions. EZH2 represses proliferation checkpoint genes and helps establish bivalent ch...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2013.04.011

    authors: Béguelin W,Popovic R,Teater M,Jiang Y,Bunting KL,Rosen M,Shen H,Yang SN,Wang L,Ezponda T,Martinez-Garcia E,Zhang H,Zheng Y,Verma SK,McCabe MT,Ott HM,Van Aller GS,Kruger RG,Liu Y,McHugh CF,Scott DW,Chung YR,Kel

    更新日期:2013-05-13 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

  • Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling of anti-angiogenic drugs.

    abstract::Current strategies combining anti-angiogenic drugs with chemotherapy provide clinical benefit in cancer patients. It is assumed that anti-angiogenic drugs, such as bevacizumab, transiently normalize abnormal tumor vasculature and contribute to improved delivery of subsequent chemotherapy. To investigate this concept, ...

    journal_title:Cancer cell

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.ccr.2011.11.023

    authors: Van der Veldt AA,Lubberink M,Bahce I,Walraven M,de Boer MP,Greuter HN,Hendrikse NH,Eriksson J,Windhorst AD,Postmus PE,Verheul HM,Serné EH,Lammertsma AA,Smit EF

    更新日期:2012-01-17 00:00:00

  • Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity.

    abstract::Slit is a secreted protein known to function through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, and as an inhibitor in leukocyte chemotaxis. Here we show Slit2 expression in a large number of solid tumors and Robo1 expression in vascular endothelial cells. Recombinant S...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/s1535-6108(03)00164-8

    authors: Wang B,Xiao Y,Ding BB,Zhang N,Yuan Xb,Gui L,Qian KX,Duan S,Chen Z,Rao Y,Geng JG

    更新日期:2003-07-01 00:00:00

  • Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases.

    abstract::The recent landmark Phase III clinical trial with a VEGF-specific antibody suggests that antiangiogenic therapy must be combined with cytotoxic therapy for the treatment of solid tumors. However, there are no guidelines for optimal scheduling of these therapies. Here we show that VEGFR2 blockade creates a "normalizati...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2004.10.011

    authors: Winkler F,Kozin SV,Tong RT,Chae SS,Booth MF,Garkavtsev I,Xu L,Hicklin DJ,Fukumura D,di Tomaso E,Munn LL,Jain RK

    更新日期:2004-12-01 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

  • E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer.

    abstract::Deregulation of E2F1 activity and resistance to TGFbeta are hallmarks of gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs frequently misregulated in human malignancies. Here we provide evidence that the miR-106b-25 cluster, upregulated in a subset of human gastric tumors, is activated by E2F1 in parallel wi...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2008.02.013

    authors: Petrocca F,Visone R,Onelli MR,Shah MH,Nicoloso MS,de Martino I,Iliopoulos D,Pilozzi E,Liu CG,Negrini M,Cavazzini L,Volinia S,Alder H,Ruco LP,Baldassarre G,Croce CM,Vecchione A

    更新日期:2008-03-01 00:00:00

  • PML/RARalpha targets promoter regions containing PU.1 consensus and RARE half sites in acute promyelocytic leukemia.

    abstract::PML/RARalpha is of crucial importance in acute promyelocytic leukemia (APL) both pathologically and therapeutically. Using a genome-wide approach, we identified in vivo PML/RARalpha binding sites in a PML/RARalpha-inducible cell model. Of the 2979 targeted regions, >62% contained canonical PU.1 motifs and >84% of thes...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2009.12.045

    authors: Wang K,Wang P,Shi J,Zhu X,He M,Jia X,Yang X,Qiu F,Jin W,Qian M,Fang H,Mi J,Yang X,Xiao H,Minden M,Du Y,Chen Z,Zhang J

    更新日期:2010-02-17 00:00:00

  • Stressing Out about Cancer Immunotherapy.

    abstract::Stress has long been suspected to negatively influence cancer mortality, yet the molecular mechanisms responsible for this effect have only recently been identified. A new study identifies a stress-induced response in dendritic cells-the activation of the glucocorticoid-inducible transcriptional regulator TSC22D3-as a...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.ccell.2019.10.013

    authors: He XY,Ng D,Van Aelst L,Egeblad M

    更新日期:2019-11-11 00:00:00

  • Same Script, Different Cast: Different Cell Origins Shape Molecular Features and Therapeutic Response in Glioblastoma.

    abstract::Glioblastoma is heterogeneous in the molecular subtypes based on transcriptomic classification. In this issue of Cancer Cell, Wang et al. define a cell-lineage-based stratification model for glioblastoma, highlighting how the cell of origin generates distinct molecular landscapes and therapeutic vulnerabilities from i...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2020.08.012

    authors: Wu S,Mischel PS

    更新日期:2020-09-14 00:00:00

  • A tell-tail sign of chromatin: histone mutations drive pediatric glioblastoma.

    abstract::Recent genomic analyses of pediatric glioblastoma, a poorly understood tumor with dismal outcome, have identified mutations in histone H3 variants that affect critical amino acids in the tail. The findings extend discoveries of chromatin regulator inactivation and gain-of-function mutations by documenting alteration o...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2012.03.001

    authors: Rheinbay E,Louis DN,Bernstein BE,Suvà ML

    更新日期:2012-03-20 00:00:00

  • Next-generation genomic profiling of hepatocellular adenomas: a new era of individualized patient care.

    abstract::Hepatocellular adenomas (HCAs) are clinically relevant benign liver lesions that commonly occur in women on hormonal contraceptives. In this issue of Cancer Cell, Pilati and colleagues present an integrative multi-"omics"-based analysis of HCA and identify recurrent genetic alterations associated with adenoma-carcinom...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2014.03.032

    authors: Marquardt JU,Thorgeirsson SS

    更新日期:2014-04-14 00:00:00

  • The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells.

    abstract::Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and a...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2012.03.014

    authors: Harris WJ,Huang X,Lynch JT,Spencer GJ,Hitchin JR,Li Y,Ciceri F,Blaser JG,Greystoke BF,Jordan AM,Miller CJ,Ogilvie DJ,Somervaille TC

    更新日期:2012-04-17 00:00:00

  • ATMIN is required for maintenance of genomic stability and suppression of B cell lymphoma.

    abstract::Defective V(D)J rearrangement of immunoglobulin heavy or light chain (IgH or IgL) or class switch recombination (CSR) can initiate chromosomal translocations. The DNA-damage kinase ATM is required for the suppression of chromosomal translocations but ATM regulation is incompletely understood. Here, we show that mice l...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2011.03.022

    authors: Loizou JI,Sancho R,Kanu N,Bolland DJ,Yang F,Rada C,Corcoran AE,Behrens A

    更新日期:2011-05-17 00:00:00

  • NAD(+) supplementation as a novel approach to cURIng HCC?

    abstract::In this issue of Cancer Cell, Tummala and colleagues demonstrate that unconventional prefoldin RPB5 interactor (URI) expression in hepatocytes leads to hepatocellular carcinoma (HCC) development by interacting with L-tryptophan/kynurenine/nicotinamide adenine dinucleotide (NAD(+)) metabolism. The results suggest that ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2014.11.011

    authors: Mederacke I,Schwabe RF

    更新日期:2014-12-08 00:00:00

  • Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor.

    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

    authors: Huang J,Duran A,Reina-Campos M,Valencia T,Castilla EA,Müller TD,Tschöp MH,Moscat J,Diaz-Meco MT

    更新日期:2018-04-09 00:00:00