Abstract:
:We have recently reported that elastin microfibril interface located protein 2 (EMILIN2), an extracellular matrix (ECM) glycoprotein, triggers cell death through a direct binding to death receptors. EMILIN2 thus influences cell viability through a mechanism that is unique for an ECM molecule. In the present work, we report an additional function for this molecule. First, we identify the region responsible for the proapoptotic effects, a 90-amino acid residue-long coiled-coil fragment toward the N-terminus of the molecule. The fragment recapitulates EMILIN2 proapoptotic mechanisms. In addition, using either the full molecule or the active fragment, for the first time, we demonstrate a significant antitumoral effect in vivo, likely due to a decrease in tumor cell viability. Unexpectedly, tumors treated with EMILIN2 or the deletion mutant display a significant increase of tumor angiogenesis. In view of this novel finding, the cotreatment of the growing tumors with an antiangiogenic drug led, in most cases, to a complete regression of tumor growth. These results grant further support to recent findings that pinpoint the microenvironment as an important regulator of cell fate under both physiological and pathological conditions and disclose the possibility of using EMILIN2 fragments as potent antineoplastic tools for cancer treatment.
journal_name
Neoplasiajournal_title
Neoplasia (New York, N.Y.)authors
Mongiat M,Marastoni S,Ligresti G,Lorenzon E,Schiappacassi M,Perris R,Frustaci S,Colombatti Adoi
10.1593/neo.91930subject
Has Abstractpub_date
2010-04-01 00:00:00pages
294-304issue
4eissn
1522-8002issn
1476-5586journal_volume
12pub_type
杂志文章相关文献
NEOPLASIA文献大全abstract::Previously, we identified the transcription factor CUX1 as an important modulator of invasion and resistance to apoptosis. Expression profiles suggested that CUX1 regulates a complex transcriptional program mediating tumor progression. We aimed to identify functionally relevant targets of CUX1 by using RNA interferenc...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.10486
更新日期:2010-08-01 00:00:00
abstract::It has been proposed that the structural and numerical chromosome abnormalities recorded in breast cancer could be the result of telomere dysfunction and that telomerase is activated de novo to provide a survival mechanism curtailing further chromosomal aberrations. However, recent in vivo and in vitro data show that ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/s1476-5586(03)80009-x
更新日期:2003-03-01 00:00:00
abstract::The transforming growth factorbeta (TGFbeta) superfamily regulates a broad spectrum of biological responses throughout embryonic development and adult life, including cell proliferation and differentiation, epithelial-to-mesenchymal transition, apoptosis, and angiogenesis. TGFbeta members initiate signaling by bringin...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章,评审
doi:10.1593/neo.06472
更新日期:2006-08-01 00:00:00
abstract::p300/CBP-associated factor (PCAF) is a coactivator of the tumor suppressor, p53. PCAF participates in p53's transactivation of target genes through acetylation of both bound p53 and histones within p53 target promoters. Using microarrays, we discovered that PCAF itself is induced by p53 in a panel of breast tumor cell...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.3292
更新日期:2004-05-01 00:00:00
abstract::Metastatic dissemination of primary tumors is responsible for 90% of colorectal cancer (CRC) deaths. The presence of positive lymph nodes, which separates stage I/II from stage III CRC, is a particularly key factor in patient management. Here, we describe results of a quantitative proteomic survey to identify molecula...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.09542
更新日期:2009-09-01 00:00:00
abstract::The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR ta...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2017.02.011
更新日期:2017-05-01 00:00:00
abstract::Malignant gliomas are refractory to conventional therapies, including surgery, radiotherapy and chemotherapy. Thus, a variety of therapies such as the inhibition of angiogenesis and signal transduction pathways have been attempted. In the present study, we have evaluated the combined effect of endostatin, an inhibitor...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900271
更新日期:2002-11-01 00:00:00
abstract::The maspin gene is not expressed in normal human pancreas, but its expression is acquired during human pancreatic carcinogenesis. In other normal human cells and their malignant counterparts, maspin expression is controlled through the epigenetic state of its promoter. In studies presented herein, we used bisulfite ge...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/s1476-5586(03)80045-3
更新日期:2003-09-01 00:00:00
abstract::Cancer cells can undergo stress-induced premature senescence, which is considered to be a desirable outcome of anticancer treatment. However, the escape from senescence and cancer cell repopulation give rise to some doubts concerning the effectiveness of the senescence-induced anticancer therapy. Similarly, it is post...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2015.11.008
更新日期:2015-12-01 00:00:00
abstract::Tel is an Ets transcription factor that is the target of chromosome translocations in lymphoid and myeloid leukemias and in solid tumors. It contains two functional domains, a pointed oligomerization domain and a DNA-binding domain. Retroviral transduction of a wild-type Tel cDNA into a clonal subline of NIH3T3 fibrob...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900064
更新日期:1999-12-01 00:00:00
abstract::Direct tumor injections of (CpG ODN) into murine colon tumor 26 (CT-26) tumors can induce a potent antitumor response. Tumor size at the beginning of treatment determines the final therapeutic outcome, with smaller tumors responding favorably to CpG ODN therapy whereas large tumors do not. CpG ODN injections in small ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.04166
更新日期:2004-09-01 00:00:00
abstract::For improved tumor staging and therapy control, imaging biomarkers are of great interest allowing a noninvasive characterization of invasiveness. In squamous epithelial skin and cervix lesions, transition to invasive stages is associated with enhanced matrix metalloproteinase (MMP) activity, increased angiogenesis, an...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2014.03.005
更新日期:2014-03-01 00:00:00
abstract::The genetic mechanisms underlying adrenocortical tumor development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix SNP 6.0) to detect copy number alterations (CNAs) and copy-neutral losses of heterozygosity (cnLOH) in 15 cortisol-secreting adrenocortical adenom...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.111758
更新日期:2012-03-01 00:00:00
abstract::High microvascular density (MVD) in the primary tumor has been shown to be associated with increased incidence of lymph node metastases and poor clinical outcome. Other investigations have revealed that a large fraction of hypoxic tissue in the primary tumor is associated with metastatic disease and impaired survival....
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2014.07.003
更新日期:2014-07-01 00:00:00
abstract::Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-sc...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.111574
更新日期:2012-01-01 00:00:00
abstract::We report that daurinol, a novel arylnaphthalene lignan, is a promising potential anticancer agent with adverse effects that are less severe than those of etoposide, a clinical anticancer agent. Despite its potent antitumor activity, clinical use of etoposide is limited because of its adverse effects, including myelos...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.11972
更新日期:2011-11-01 00:00:00
abstract::The present study focuses on the influence of the tumor microenvironment on the expression of HLA-G in ovarian cancer and its impact on immune cells. We used carcinomatosis fluids (n = 16) collected from patients diagnosed with epithelial ovarian cancer, detected by an increase in CA125 levels. Our results indicate th...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2019.01.001
更新日期:2019-03-01 00:00:00
abstract::Recent studies have established that a significant fraction of prostate cancers harbor a signature gene fusion between the 5' region of androgen-regulated TMPRSS2 and an ETS family transcription factor, most commonly ERG. Studies on the molecular mechanisms and functional consequences of this important chromosomal rea...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07103
更新日期:2007-03-01 00:00:00
abstract::A significant proportion of colorectal adenomas, in particular those that lack an elevated growth component, continue to escape detection during endoscopic surveillance. Elevation of the activity of matrix metalloproteinases (MMPs), a large family of zinc endopeptidases, in adenomas serves as a biomarker of early tumo...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.11400
更新日期:2011-08-01 00:00:00
abstract::Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whet...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2015.09.003
更新日期:2015-09-01 00:00:00
abstract::Cancers originating from epithelial cells are the most common malignancies. No common expression profile of solid tumors compared to normal tissues has been described so far. Therefore we were interested if genes differentially expressed in the majority of carcinomas could be identified using bioinformatic methods. Co...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.04277
更新日期:2004-11-01 00:00:00
abstract::Tumor cells in the bone interact with the microenvironment to promote tumor cell survival and proliferation, resulting in a lethal phenotype for patients with advanced prostate cancer. Monocyte chemoattractant protein 1 (CCL2) is a member of the CC chemokine family and is known to promote monocyte chemotaxis to sites ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.06280
更新日期:2006-07-01 00:00:00
abstract:PURPOSE:Upregulation of Bcl-2 family members is a well-established mechanism in the development of androgen-independent prostate cancer. Inhibition of the antiapoptotic proteins Bcl-2 and Mcl-1 may delay the transition to androgen-independent growth. EXPERIMENTAL DESIGN:We have established a prostate cancer model with...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07778
更新日期:2007-12-01 00:00:00
abstract::While normal cells in the human breast are organized into acinar structures, disruption of the acinar architecture is a hallmark of cancer. In a three-dimensional model of morphogenesis, we show that down-regulation of the matrix-associated tumor suppressor protein CCN6 (WNT1-inducible-signaling pathway protein 3) dis...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.121322
更新日期:2012-11-01 00:00:00
abstract::Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4) in medulloblastoma using high-resolution single nucleotide polymorphism arrays, digital karyotyping, and ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.91122
更新日期:2010-01-01 00:00:00
abstract::Adenosine monophosphate-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis, has emerged as a promising molecular target in the prevention of breast cancer. Clinical trials using the United States Food and Drug Administration (FDA)-approved, AMPK-activating, antidiabetic drug metformin a...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.131434
更新日期:2013-12-01 00:00:00
abstract::Lung adenocarcinoma (LAD) is a human malignancy successfully treated with the tyrosine kinase inhibitor (TKI) gefitinib; however, the enrichment of therapy resistant cancer stem cells (CSCs) in such patients is assumed to be a source of treatment failure. Evaluation of LAD cell populations treated with the TKI inhibit...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2019.10.006
更新日期:2020-01-01 00:00:00
abstract::Glioblastomas are malignant brain tumors that are rarely curable, even with aggressive therapy (surgery, chemotherapy, and radiation). Glioblastomas frequently display loss of PTEN and/or epidermal growth factor receptor activation, both of which activate the PI3K pathway. This pathway can increase vascular endothelia...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.06535
更新日期:2006-11-01 00:00:00
abstract::To investigate the cellular/molecular basis of the activity of a novel lipophilic camptothecin, gimatecan (ST1481), against slowly proliferating cells, we performed a comparative study of topotecan and gimatecan in human bladder cancer models (HT1376 and MCR). Gimatecan was significantly more effective than topotecan ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.04397
更新日期:2005-02-01 00:00:00
abstract::It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a "CpG island methylated phenotype (CIMP)," characterized by preferential proximal location in the colon, but otherwise poorly defined. The...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.04502
更新日期:2005-04-01 00:00:00