Rapamycin inhibits F-actin reorganization and phosphorylation of focal adhesion proteins.

Abstract:

:An early event of cell migration is characterized as the rapid reorganization of the actin cytoskeleton. Recently, we have demonstrated that rapamycin inhibits tumor cell motility. To understand the underlying mechanism, this study was set to determine whether rapamycin inhibition of cell motility is related to its prevention of F-actin reorganization. We found that rapamycin prevented type I insulin-like growth factor (IGF-I)-stimulated F-actin reorganization in human rhabdomyosarcoma (Rh30), Ewing sarcoma (Rh1), glioblastoma (U-373) and prostate carcinoma (PC-3) cells, and concurrently inhibited phosphorylation of focal adhesion proteins, including focal adhesion kinase (FAK), paxillin and p130(Cas) in the cells. The effect of rapamycin was blocked by expression of a rapamycin-resistant mutant of mTOR (mTORrr), but not a kinase-dead mTORrr. Downregulation of raptor mimicked the effect of rapamycin. Cells infected with a recombinant adenovirus expressing constitutively active and rapamycin-resistant mutant of p70 S6 kinase 1 (S6K1) conferred to resistance to rapamycin. Further, IGF-I failed to stimulate F-actin reorganization and phosphorylation of the focal adhesion proteins in the S6K1-downregulated cells. Expression of constitutively hypophosphorylated eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1-5A) inhibited IGF-I-stimulated F-actin reorganization, but did not alter the cellular protein or phosphorylation levels of the focal adhesion proteins. The results suggest that rapamycin inhibits IGF-I-induced F-actin reorganization and phosphorylation of the focal adhesion proteins by disruption of mTOR-raptor complex. Both S6K1 and 4E-BP1 pathways, mediated by the mTOR-raptor complex, are involved in the regulation of IGF-I-stimulated F-actin reorganization, but only the former controls IGF-I-stimulated phosphorylation of the focal adhesion proteins.

journal_name

Oncogene

journal_title

Oncogene

authors

Liu L,Chen L,Chung J,Huang S

doi

10.1038/onc.2008.137

subject

Has Abstract

pub_date

2008-08-28 00:00:00

pages

4998-5010

issue

37

eissn

0950-9232

issn

1476-5594

pii

onc2008137

journal_volume

27

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Epigenetic patterns of the retinoic acid receptor beta2 promoter in retinoic acid-resistant thyroid cancer cells.

    abstract::Treatment with retinoic acid (RA) is effective to restore radioactive iodine uptake in metastases of a small fraction of thyroid cancer patients. In order to find predictive markers of response, we took advantage of two thyroid cancer cell lines, FTC133 and FTC238, with low RA-receptor (RAR)beta expression but differi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210178

    authors: Cras A,Darsin-Bettinger D,Balitrand N,Cassinat B,Soulié A,Toubert ME,Delva L,Chomienne C

    更新日期:2007-06-07 00:00:00

  • TBX2 interacts with heterochromatin protein 1 to recruit a novel repression complex to EGR1-targeted promoters to drive the proliferation of breast cancer cells.

    abstract::Early Growth Response 1 (EGR1) is a stress response transcription factor with multiple tumour suppressor roles in breast tissue, whose expression is often lost in breast cancers. We have previously shown that the breast cancer oncogene TBX2 (T-BOX2) interacts with EGR1 to co-repress EGR1-target genes including the bre...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0853-z

    authors: Crawford NT,McIntyre AJ,McCormick A,D'Costa ZC,Buckley NE,Mullan PB

    更新日期:2019-08-01 00:00:00

  • Autocrine HGF/c-Met signaling pathway confers aggressiveness in lymph node adult T-cell leukemia/lymphoma.

    abstract::Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm. While ATL cells in peripheral blood (PB-ATL) are sensitive to anti-CC chemokine receptor 4 treatment, non-PB-ATLs, including lymph node ATLs (LN-ATLs), are more aggressive and resistant. We examined characteristic cytokines and growth factors that ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-01393-x

    authors: Totani H,Shinjo K,Suzuki M,Katsushima K,Mase S,Masaki A,Ito A,Ri M,Kusumoto S,Komatsu H,Ishida T,Inagaki H,Iida S,Kondo Y

    更新日期:2020-08-01 00:00:00

  • Multimerin-2 is a ligand for group 14 family C-type lectins CLEC14A, CD93 and CD248 spanning the endothelial pericyte interface.

    abstract::The C-type lectin domain containing group 14 family members CLEC14A and CD93 are proteins expressed by endothelium and are implicated in tumour angiogenesis. CD248 (alternatively known as endosialin or tumour endothelial marker-1) is also a member of this family and is expressed by tumour-associated fibroblasts and pe...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.214

    authors: Khan KA,Naylor AJ,Khan A,Noy PJ,Mambretti M,Lodhia P,Athwal J,Korzystka A,Buckley CD,Willcox BE,Mohammed F,Bicknell R

    更新日期:2017-11-02 00:00:00

  • Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness.

    abstract::Amplified in breast cancer 1 (AIB1) is a transcriptional coactivator for nuclear receptors and other transcription factors. AIB1 has an important role in malignancy of several cancers such as breast and prostate cancers. However, its involvement in human hepatocellular carcinoma (HCC) progression remains unclear. Here...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.90

    authors: Xu Y,Chen Q,Li W,Su X,Chen T,Liu Y,Zhao Y,Yu C

    更新日期:2010-06-10 00:00:00

  • Mutant p53: an oncogenic transcription factor.

    abstract::Inactivation of tumor-suppressor genes is one of the key hallmarks of a tumor. Unlike other tumor-suppressor genes, p53 is inactivated by missense mutations in half of all human cancers. It has become increasingly clear that the resulting mutant p53 proteins do not represent only the mere loss of wild-type p53 tumor s...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1210296

    authors: Strano S,Dell'Orso S,Di Agostino S,Fontemaggi G,Sacchi A,Blandino G

    更新日期:2007-04-02 00:00:00

  • A role for Myc in facilitating transcription activation by E2F1.

    abstract::Previous work has demonstrated that E2F proteins regulate the expression of various genes encoding proteins essential for DNA replication and cell-cycle progression. E2F1 in particular is required for the initial entry to the cell cycle from a quiescent state and is required for the activation of other E2F genes. Othe...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.55

    authors: Leung JY,Ehmann GL,Giangrande PH,Nevins JR

    更新日期:2008-07-10 00:00:00

  • Expression of the naturally occurring truncated trkB neurotrophin receptor induces outgrowth of filopodia and processes in neuroblastoma cells.

    abstract::We have investigated the effects of the truncated trkB receptor isoform T1 (trkB.T1) by transient transfection into mouse N2a neuroblastoma cells. We observed that expression of trkB.T1 leads to a striking change in cell morphology characterized by outgrowth of filopodia and processes. A similar morphological response...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202401

    authors: Haapasalo A,Saarelainen T,Moshnyakov M,Arumäe U,Kiema TR,Saarma M,Wong G,Castrén E

    更新日期:1999-02-11 00:00:00

  • Translation of p15.5INK4B, an N-terminally extended and fully active form of p15INK4B, is initiated from an upstream GUG codon.

    abstract::The expression of the cyclin-dependent kinase inhibitor p15INK4B in normal cells after induction with TGF-beta1, or following overexpression from an adenovirus-encoded cDNA, appears on an SDS-polyacrylamide gel as a doublet. Here, the underlying mechanism behind the synthesis of the two species has been studied. By ex...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203496

    authors: Fuxe J,Raschperger E,Pettersson RF

    更新日期:2000-03-23 00:00:00

  • Suppression of Tumorigenicity-14, encoding matriptase, is a critical suppressor of colitis and colitis-associated colon carcinogenesis.

    abstract::Colitis-associated colorectal cancers are an etiologically distinct subgroup of colon cancers that occur in individuals suffering from inflammatory bowel disease and arise as a consequence of persistent exposure of hyperproliferative epithelial stem cells to an inflammatory microenvironment. An intrinsic defect in the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.545

    authors: Kosa P,Szabo R,Molinolo AA,Bugge TH

    更新日期:2012-08-09 00:00:00

  • miR-34a functions as a tumor suppressor modulating EGFR in glioblastoma multiforme.

    abstract::Chromosome 1p36.23 is frequently deleted in glioblastoma multiforme (GBM). miR-34a localizes in this region. Our experiments found that miR-34a was often deleted and epidermal growth factor receptor (EGFR) was frequently amplified in genomic DNA of 55 GBMs using single-nucleotide polymorphism DNA microarray. Notably, ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.132

    authors: Yin D,Ogawa S,Kawamata N,Leiter A,Ham M,Li D,Doan NB,Said JW,Black KL,Phillip Koeffler H

    更新日期:2013-02-28 00:00:00

  • LCE: an open web portal to explore gene expression and clinical associations in lung cancer.

    abstract::We constructed a lung cancer-specific database housing expression data and clinical data from over 6700 patients in 56 studies. Expression data from 23 genome-wide platforms were carefully processed and quality controlled, whereas clinical data were standardized and rigorously curated. Empowered by this lung cancer da...

    journal_title:Oncogene

    pub_type: 杂志文章,meta分析

    doi:10.1038/s41388-018-0588-2

    authors: Cai L,Lin S,Girard L,Zhou Y,Yang L,Ci B,Zhou Q,Luo D,Yao B,Tang H,Allen J,Huffman K,Gazdar A,Heymach J,Wistuba I,Xiao G,Minna J,Xie Y

    更新日期:2019-04-01 00:00:00

  • Role of the adaptor protein LNK in normal and malignant hematopoiesis.

    abstract::The signal transduction pathways, orchestrating the differentiation of hematopoietic stem and progenitor cells in response to cytokine stimulation, are strictly controlled by networks of feedback loops, highly selective protein interactions and finely tuned on/off switches. In hematological malignancies, the aberrant ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2012.435

    authors: Gery S,Koeffler HP

    更新日期:2013-06-27 00:00:00

  • Decreased BRCA1 confers tamoxifen resistance in breast cancer cells by altering estrogen receptor-coregulator interactions.

    abstract::The breast cancer susceptibility gene 1 (BRCA1) is mutated in approximately 50% of hereditary breast cancers, and its expression is decreased in 30-40% of sporadic breast cancers, suggesting a general role in breast cancer development. BRCA1 physically and functionally interacts with estrogen receptor-alpha (ERalpha) ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.405

    authors: Wen J,Li R,Lu Y,Shupnik MA

    更新日期:2009-01-29 00:00:00

  • Identification of a dominant-negative mutation in the yeast CDC25 guanine nucleotide exchange factor for Ras.

    abstract::In previous studies we changed five conserved amino acid residues in the catalytic domain of the yeast Ras-specific guanine nucleotide exchange factor CDC25GEF (Park et al., 1994). One of the substitutions (R1489E) resulted in a molecule which could bind Ras but was catalytically inactive. These observations suggested...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1200893

    authors: Park W,Mosteller RD,Broek D

    更新日期:1997-02-20 00:00:00

  • Overexpression of wild-type p53 interferes with normal development in Xenopus laevis embryos.

    abstract::We have cloned and sequenced a Xenopus p53 homologue which differs by one amino acid deletion from a previously published Xenopus sequence (Soussi et al., 1987). Transcription analysis revealed that this gene is activated during early oogenesis and that zygotic transcription initiates after midblastula transition. Tra...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Hoever M,Clement JH,Wedlich D,Montenarh M,Knöchel W

    更新日期:1994-01-01 00:00:00

  • Combined effects of the two reciprocal t(4;11) fusion proteins MLL.AF4 and AF4.MLL confer resistance to apoptosis, cell cycling capacity and growth transformation.

    abstract::The reciprocal chromosomal translocation t(4;11) is correlated with infant, childhood, adult and therapy-related high-risk acute leukemia. Here, we investigated the biological effects of MLL.AF4, AF4.MLL or the combination of both reciprocal fusion proteins in a conditional in vitro cell culture model system. Several ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210125

    authors: Gaussmann A,Wenger T,Eberle I,Bursen A,Bracharz S,Herr I,Dingermann T,Marschalek R

    更新日期:2007-05-17 00:00:00

  • Dissecting the role of TGF-beta type I receptor/ALK5 in pancreatic ductal adenocarcinoma: Smad activation is crucial for both the tumor suppressive and prometastatic function.

    abstract::In the present study, we have analysed the effects of transforming growth factor-beta (TGF-beta) signaling on the growth behavior of pancreatic carcinoma cells in vitro and on their tumorigenicity in vivo. Ectopic expression of dominant-negative mutants of the TGF-beta type II receptor or type I receptor/activin recep...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210272

    authors: Schniewind B,Groth S,Sebens Müerköster S,Sipos B,Schäfer H,Kalthoff H,Fändrich F,Ungefroren H

    更新日期:2007-07-19 00:00:00

  • The human papillomavirus E6 protein and its contribution to malignant progression.

    abstract::The human papillomavirus (HPV) E6 protein is one of three oncoproteins encoded by the virus. It has long been recognized as a potent oncogene and is intimately associated with the events that result in the malignant conversion of virally infected cells. In order to understand the mechanisms by which E6 contributes to ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1204869

    authors: Mantovani F,Banks L

    更新日期:2001-11-26 00:00:00

  • N-cadherin regulates mammary tumor cell migration through Akt3 suppression.

    abstract::N-cadherin is a cell-cell adhesion molecule that plays a role in breast cancer metastasis. Here, we show that in vivo expression of N-cadherin in the PyMT mouse model, which enhances mammary tumor metastasis, results in selective inhibition of Akt3 expression and phosphorylation. Similarly, exogenous expression of N-c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.65

    authors: Chung S,Yao J,Suyama K,Bajaj S,Qian X,Loudig OD,Eugenin EA,Phillips GR,Hazan RB

    更新日期:2013-01-24 00:00:00

  • GSK3 beta mediates suppression of cyclin D2 expression by tumor suppressor PTEN.

    abstract::PTEN, encoding a lipid phosphatase, is a tumor suppressor gene and is mutated in various types of cancers. It is reported to regulate G1 to S phase transition of the cell cycle by influencing the expression, protein stability and subcellular location of cyclin D1. Here, we provide evidence that PTEN modulates the tran...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210033

    authors: Huang W,Chang HY,Fei T,Wu H,Chen YG

    更新日期:2007-04-12 00:00:00

  • A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer.

    abstract::Targeted cancer therapies, although often effective, have limited utility owing to preexisting primary or acquired secondary resistance. Consequently, agents are sometimes used in combination to simultaneously affect multiple targets. MicroRNA mimics are excellent therapeutic candidates because of their ability to rep...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.282

    authors: Kasinski AL,Kelnar K,Stahlhut C,Orellana E,Zhao J,Shimer E,Dysart S,Chen X,Bader AG,Slack FJ

    更新日期:2015-07-01 00:00:00

  • Skp2-mediated ubiquitination and mitochondrial localization of Akt drive tumor growth and chemoresistance to cisplatin.

    abstract::The E3 ligase S-phase kinase-associated protein 2(Skp2) is overexpressed in human cancers and correlated with poor prognosis, but its contributions to tumorigenesis and chemoresistance in nasopharyngeal carcinoma (NPC) are not evident. Herein we show that Skp2 is highly expressed in NPC tumor tissues and cell lines. K...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0955-7

    authors: Yu X,Wang R,Zhang Y,Zhou L,Wang W,Liu H,Li W

    更新日期:2019-12-01 00:00:00

  • MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13.

    abstract::Recently, the MLL gene at 11q23 was found to be involved in a subset of leukemias with an 11q23 abnormality. In the present study, we isolated chimeric cDNAs between the MLL and a gene designated MLLT3 at 9p22 from a cDNA library of an IMS-M1 cell line with a t(9;11)(p22;q23) translocation, a representative karyotypic...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Iida S,Seto M,Yamamoto K,Komatsu H,Tojo A,Asano S,Kamada N,Ariyoshi Y,Takahashi T,Ueda R

    更新日期:1993-11-01 00:00:00

  • P-Rex1 participates in Neuregulin-ErbB signal transduction and its expression correlates with patient outcome in breast cancer.

    abstract::The Neuregulins and their receptors, the ErbB/HER subfamily of receptor tyrosine kinases, have critical roles in animal physiology, and their deregulation is frequent in cancer. Here we report the identification of the guanine nucleotide exchange factor, phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchanger ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.489

    authors: Montero JC,Seoane S,Ocaña A,Pandiella A

    更新日期:2011-03-03 00:00:00

  • Extramammary Paget's disease patient-derived xenografts harboring ERBB2 S310F mutation show sensitivity to HER2-targeted therapies.

    abstract::Although the prognosis of advanced extramammary Paget's disease (EMPD) is poor, there have been no preclinical research models for the development of novel therapeutics. This study aims to establish a preclinical research model for EMPD. We transplanted EMPD tissue into immunodeficient NOD/Scid mice. Histopathological...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-01404-x

    authors: Maeda T,Kitamura S,Nishihara H,Yanagi T

    更新日期:2020-09-01 00:00:00

  • Alternatively spliced HPV-18 E6* protein inhibits E6 mediated degradation of p53 and suppresses transformed cell growth.

    abstract::The E6 proteins originating from the tumour-associated Human Papillomavirus (HPV) types 16 and 18 have been shown to bind to and target the tumour suppressor protein, p53, for ubiquitin-mediated degradation. However, in cell lines derived from cervical neoplasias, the predominant early region transcripts are spliced a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201202

    authors: Pim D,Massimi P,Banks L

    更新日期:1997-07-17 00:00:00

  • FYN promotes mesenchymal phenotypes of basal type breast cancer cells through STAT5/NOTCH2 signaling node.

    abstract::Basal type breast cancer is the most aggressive and has mesenchymal features with a high metastatic ability. However, the signaling node that determines the basal type features in breast cancer remains obscure. Here, we report that FYN among SRC family kinases is required for the maintenance of basal type breast cance...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-017-0114-y

    authors: Lee GH,Yoo KC,An Y,Lee HJ,Lee M,Uddin N,Kim MJ,Kim IG,Suh Y,Lee SJ

    更新日期:2018-04-01 00:00:00

  • Proviral integrations at the Evi5 locus disrupt a novel 90 kDa protein with homology to the Tre2 oncogene and cell-cycle regulatory proteins.

    abstract::Evi5 is a common site of retroviral integration in T-cell lymphomas of AKXD mice. Mapping studies have localized Evi5 to a region approximately 18 kb upstream of another common viral integration site, Gfi1, on mouse chromosome 5 (Liao X, Jenkins NA and Copeland NG, (1995a). J. Virol., 69, 7132-7137). Gfi1 encodes a zi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1200929

    authors: Liao X,Du Y,Morse HC 3rd,Jenkins NA,Copeland NG

    更新日期:1997-03-06 00:00:00

  • Future prospects for oncolytic therapy.

    abstract::Viruses have been engineered to replicate selectively in cancer cells, based on a number of innovative principles. Several of these viruses have entered clinical trials and have proven relatively safe, and have shown evidence of efficacy. However, further research is required to enable these agents to function systemi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209064

    authors: McCormick F

    更新日期:2005-11-21 00:00:00