Abstract：
:Cancer cell survival is frequently dependent on the elevated levels of members of the Bcl-2 family of prosurvival proteins that bind to and inactivate BH3-domain pro-apoptotic cellular proteins. Small molecules that inhibit the protein-protein interactions between prosurvival and proapoptotic Bcl-2 family members (so-called "BH3 mimetics") have a potential therapeutic value, as indicated by clinical findings obtained with ABT-263 (navitoclax), a Bcl-2/Bcl-xL antagonist, and more recently with GDC-0199/ABT-199, a more selective antagonist of Bcl-2. Here, we report study results of the functional role of the prosurvival protein Mcl-1 against a panel of solid cancer cell lines representative of different tumor types. We observed silencing of Mcl-1 expression by small interfering RNAs (siRNAs) significantly reduced viability and induced apoptosis in almost 30% of cell lines tested, including lung and breast adenocarcinoma, as well as glioblastoma derived lines. Most importantly, we provide a mechanistic basis for this sensitivity by showing antagonism of Mcl-1 function with specific BH3 peptides against isolated mitochondria induces Bak oligomerization and cytochrome c release, therefore demonstrating that mitochondria from Mcl-1-sensitive cells depend on Mcl-1 for their integrity and that antagonizing Mcl-1 function is sufficient to induce apoptosis. Thus, our results lend further support for considering Mcl-1 as a therapeutic target in a number of solid cancers and support the rationale for development of small molecule BH3-mimetics antagonists of this protein.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Modugno M,Banfi P,Gasparri F,Borzilleri R,Carter P,Cornelius L,Gottardis M,Lee V,Mapelli C,Naglich JG,Tebben A,Vite G,Pastori W,Albanese C,Corti E,Ballinari D,Galvani Adoi
10.1016/j.yexcr.2014.11.022subject
Has Abstractpub_date
2015-03-15 00:00:00pages
267-77issue
2eissn
0014-4827issn
1090-2422pii
S0014-4827(14)00525-4journal_volume
332pub_type
杂志文章abstract：:14-3-3 proteins are a family of homologous eukaryotic molecules with seven distinct isoforms in mammalian cells. Isoforms of 14-3-3 proteins interact with diverse ligands and are involved in the regulation of mitogenesis, cell cycle progression, and apoptosis. However, whether different 14-3-3 isoforms are responsible...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.2001.5376
更新日期：2001-11-15 00:00:00
abstract：:The c-Myb transcription factor plays a central role in the regulation of cell growth and differentiation of hematopoietic cells. Being the product of a proto-oncogene, one would expect c-Myb function to be modulated by signal transduction pathways, but our knowledge on such regulation of c-Myb is rather limited. Recen...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2004.03.014
更新日期：2004-07-01 00:00:00
abstract：:In many systems, events participating in cell division are controlled by intracellular pH (pHi). In Xenopus eggs, fertilization is accompanied by an increase in pHi which occurs concomitantly with an increase in protein synthesis and a reinitiation of DNA synthesis, leading the embryo to cell division. In this paper, ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(89)90313-3
更新日期：1989-12-01 00:00:00
abstract：:The effect of hydrocortisone (HC) on PDGF beta-receptor expression was studied in the human malignant mesothelioma cell line Mero-14. HC was found to induce a time- and dose-dependent increase of PDGF beta-receptor mRNA. Nuclear run off analysis revealed that HC induced increased transcription of the PDGF beta-recepto...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/s0014-4827(05)80074-6
更新日期：1992-05-01 00:00:00
abstract：:Dominant mutations in presenilin1 (PS1) and presenilin2 (PS2) are a major cause of early-onset Alzheimer's disease. In this report we analyze the expression of the zebrafish presenilin1 (Psen1) and presenilin2 (Psen2) proteins during embryogenesis. We demonstrate that Psen1 and Psen2 holoproteins are relatively abunda...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/s0014-4827(03)00257-x
更新日期：2003-09-10 00:00:00
abstract：:Microglia, the parenchymal immune cells of the central nervous system, orchestrate neuroinflammation in response to infection or damage, and promote tissue repair. However, aberrant microglial responses are integral to neurodegenerative diseases and critically contribute to disease progression. Thus, it is important t...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2019.02.023
更新日期：2019-04-15 00:00:00
abstract：:The characterization of a mucus-producing human cell line (HC-84) derived from a colon carcinoma and its response to in vitro reserpine treatment is reported. Mucous granules were demonstrated within these cells on the basis of electron microscopic examination and incorporation of [3H]glucosamine with subsequent autor...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(84)90709-2
更新日期：1984-01-01 00:00:00
abstract：:An implantation-competent blastocyst, several hours prior to its attachment on the uterine wall, transmits signals to surrounding uterine cells and vice-versa to initiate a two-way interaction. The language of this precocious dialogue is versatile, taking advantage of secreted molecules for long-range interactions and...
journal_title：Experimental cell research
pub_type： 杂志文章,评审
doi：10.1016/j.yexcr.2008.07.025
更新日期：2009-02-15 00:00:00
abstract：:The Alternative Reading Frame (ARF) protein suppresses tumorigenesis through p53-dependent and p53-independent pathways. Most of ARF's anti-proliferative activity is conferred by sequences in its first exon. Previous work showed specific amino acid changes occurred in that region during primate evolution, so we progra...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2009.01.010
更新日期：2009-04-15 00:00:00
abstract：:Eps8 controls actin dynamics directly through its barbed end capping and actin-bundling activity, and indirectly by regulating Rac-activation when engaged into a trimeric complex with Eps8-Abi1-Sos1. Recently, Eps8 has been associated with promotion of various solid malignancies, but neither its mechanisms of action n...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2010.02.020
更新日期：2010-07-15 00:00:00
abstract：:Rhabdomyosarcoma (RMS) are soft-tissue sarcoma commonly encountered in childhood. RMS cells can acquire invasive behavior and form metastases. The metastatic dissemination implicates many proteases among which are mu-calpain and m-calpain. Study of calpain expression and activity underline the deregulation of calpain ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2010.02.017
更新日期：2010-05-15 00:00:00
abstract：:Current methods of monitoring insulin in culture are limited to soluble insulin (secretions or lysates) or synthetic gene reporter analyses. We present an insulin-specific cell enzyme-linked immunosorbent assay (cell-ELISA) to assess relative intracellular insulin protein content of adherent cultures, normalized to ce...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2016.06.014
更新日期：2016-09-10 00:00:00
abstract：:Epithelial-mesenchymal transition (EMT) plays an important role in breast cancer cell metastasis. Both (megakaryoblastic leukemia)/myocardin-like 1 (MKL-1) and Signal transducer and activator of transcription 3 (STAT3) have been implicated in the control of cellular metabolism, survival and growth. Our previous study ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2017.05.007
更新日期：2017-08-01 00:00:00
abstract：:Elongation factor-1 delta gene expression was analyzed during sea urchin development. EF-1 delta mRNA is present as a single 2.7-kb transcript in unfertilized eggs and in rapidly dividing cleavage stage embryos. It decreases rapidly 6 h after fertilization and then reappears at the gastrula stage as two transcripts of...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1998.4104
更新日期：1998-07-10 00:00:00
abstract：:Recruitment of mesenchymal stem cells (MSC) to tissue damages is a promising approach for in situ tissue regeneration. The physiological mechanisms and regulatory processes of MSC trafficking to injured tissue remain poorly understood. However, the pivotal role of chemokines in MSC recruitment has already been shown. ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2008.12.022
更新日期：2009-05-01 00:00:00
abstract：:Inorganic polyphosphate [Poly(P)] may represent a physiological source of phosphate and has the ability to induce bone differentiation in osteoblasts. We previously reported that cytokine-induced matrix metalloproteinase (MMP)-3 accelerates the proliferation of purified odontoblast-like cells. In this study, MMP-3 sma...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2015.01.007
更新日期：2015-05-01 00:00:00
abstract：:Thyroid hormone (T3) and estradiol (Est) modulate biological processes by binding to nuclear receptor proteins that, through interactions with specific response elements in the regulatory regions of genes, modulate gene transcription. Est stimulation of estrogen receptor (ER)-positive breast carcinoma cell growth occu...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1995.1124
更新日期：1995-05-01 00:00:00
abstract：:The effect of 1 microM antimycin on the proliferative properties, metabolism and basic cell composition of Ehrlich ascites tumour cells cultured in the second in vitro passage was studied. Continuous drug exposure of asynchronous cells caused rapid cessation of cell growth, characterized by the cell number and DNA, RN...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(85)90162-4
更新日期：1985-03-01 00:00:00
abstract：:Melanotransferrin is a glycoprotein expressed at the cell membrane and secreted in the extracellular environment. Recombinant truncated form of membrane-bound melanotransferrin (sMTf) was reported to exert in vitro anti-angiogenic properties. Here we show that sMTf treatment leads to a 50% inhibition of neovasculariza...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2007.04.013
更新日期：2007-08-01 00:00:00
abstract：:In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proli...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2010.02.013
更新日期：2010-04-15 00:00:00
abstract：:Breast cancer (BC) is one of the most common cancers among women in both developed and developing countries with a rising incidence. Using the MMTV-PyMT transgenic mouse model and xenografted breast cancer model, we found that R5, a neutralizing antibody to Robo1, significantly inhibited BC growth and metastasis. Angi...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2019.111756
更新日期：2020-02-01 00:00:00
abstract：:Histone deacetylase inhibitors (HDACi) were recently identified as having significant clinical potential in reversing β-cell functional inhibition caused by inflammation, a shared precursor of Type 1 and Type 2 diabetes. However, HDACi are highly complex and little is known of their direct effect on important cell sec...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2014.09.031
更新日期：2015-01-01 00:00:00
abstract：:Previous studies have shown that centrosome position and structure can be influenced by actin filaments, that centrosomes can influence actin organization, and that an actin homologue is associated with centrosomes. Such observations suggest the existence of connections between centrosomes and actin networks. In keepi...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1995.1245
更新日期：1995-08-01 00:00:00
abstract：:We studied the expression of FREK (fibroblast growth factor receptor-like embryonic kinase), a new receptor recently cloned from quail embryo, during the differentiation of skeletal muscle satellite cells and epiphyseal growth-plate chondrocytes. Although FREK mRNA was expressed in both cell types, satellite cells exp...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1994.1144
更新日期：1994-06-01 00:00:00
abstract：:Whey Acidic Protein (WAP) gene expression is specific to the mammary gland and regulated by lactogenic hormones to peak during lactation. It differs markedly from the more constitutive expression of the two flanking genes, Ramp3 and Tbrg4. Our results show that the tight regulation of WAP gene expression parallels var...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2008.01.001
更新日期：2008-03-10 00:00:00
abstract：:Neuromedin B (NMB) is one of the bombesin-like peptides in mammals. Recently, bombesin-like peptides have been characterized as growth factors in highly vascularized tumors. In this study, we report that NMB potently stimulates in vivo neovascularization in a mouse Matrigel plug and the sprouting of endothelial cells ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2009.08.009
更新日期：2009-11-15 00:00:00
abstract：:The effect of transferrin was tested on osteoblastic cells (clone MC3T3-E1) cultured in serum-free medium containing 1% bovine serum albumin (BSA). Transferrin (Tf) stimulated increases of protein content and protein synthesis, but not of DNA content and cell number, in the cells. This protein also increased alkaline ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(84)90465-8
更新日期：1984-07-01 00:00:00
abstract：:Transfection of primary rat keratinocytes with the polyomavirus large T gene promotes the establishment of cell lines. The keratinocytes express the large T protein and can be continuously cultured in medium containing a low concentration of calcium. The immortalized keratinocytes retain the ability to differentiate w...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(88)90042-0
更新日期：1988-07-01 00:00:00
abstract：:A great deal of evidence suggests that long non-coding RNAs (lncRNAs) function in the tumorigenesis of retinoblastoma (RB). However, the roles of lncRNA ILF3-AS1 in RB are still unclear. In the present study, our work revealed that the lncRNA ILF3-AS1 was increased in both RB tissues and cell lines. Repression of ILF3...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2020.112087
更新日期：2020-08-15 00:00:00
abstract：:Contraction of 3D collagen matrices by fibroblasts frequently is used as an in vitro model of wound closure. Different iterations of the model - all conventionally referred to as "contraction" - involve different morphological patterns. During floating matrix contraction, cells initially are round without stress fiber...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2014.04.013
更新日期：2014-08-15 00:00:00
