Abstract:
:Overexpressed or activated hepatocyte growth factor receptor, encoded by the MET proto-oncogene, was found in the majority of colorectal carcinomas (CRCs), whose stepwise progression to malignancy requires transcriptional activation of beta-catenin. We here demonstrate that a functional crosstalk between Met and beta-catenin signaling sustains and increases CRC cell invasive properties. Hepatocyte growth factor (HGF) stimulation prompts beta-catenin tyrosine phosphorylation and dissociation from Met, and upregulates beta-catenin expression via the phosphatidylinositol 3-kinase pathway in conditions that mimic those found by the invading and metastasizing cells. Additionally, a transcriptionally active form of beta-catenin, known to be oncogenic, enhances Met expression. Furthermore, HGF treatment increases the activity of the beta-catenin-regulated T-cell factor transcription factor in cells expressing the wild-type or the oncogenic beta-catenin. In the mirror experiments, either Met or beta-catenin knocking down also reduces their protein level. In biological assays, beta-catenin knocking down abrogates the HGF-induced motile phenotype, whereas active beta-catenin fosters ligand-independent cell scattering. Met and beta-catenin also cooperate in promoting entry into the cell cycle and in protecting cells from apoptosis. In conclusion, Met and beta-catenin pathways are mutually activated in CRC cells. This might generate a self-amplifying positive feedback loop resulting in the upregulation of the invasive growth properties of CRC cells.
journal_name
Oncogenejournal_title
Oncogeneauthors
Rasola A,Fassetta M,De Bacco F,D'Alessandro L,Gramaglia D,Di Renzo MF,Comoglio PMdoi
10.1038/sj.onc.1209859subject
Has Abstractpub_date
2007-02-15 00:00:00pages
1078-87issue
7eissn
0950-9232issn
1476-5594pii
1209859journal_volume
26pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Intrinsic and acquired resistance to anti-EGFR antibody therapy, frequently mediated by a mutant or amplified KRAS oncogene, is a significant challenge in the treatment of colorectal cancer (CRC). However, the mechanism of KRAS-mediated therapeutic resistance is not well understood. In this study, we demonstrate that ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0289-x
更新日期:2018-08-01 00:00:00
abstract::Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the end...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2008.309
更新日期:2008-10-27 00:00:00
abstract::Transcriptional coactivators SRC-1 and p300 specifically interact with liganded-nuclear receptors and also modulate other transcription factors, including serum response factor (SRF). Here, we report that retinoids repress transactivation by SRF and specific interactions exist between the DNA binding domains of SRF an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204695
更新日期:2001-10-04 00:00:00
abstract::While screening a chicken kidney cDNA library for the normal homolog of the yes oncogene, we isolated a clone that encodes a novel non-receptor type protein tyrosine kinase of the Src family. We named this gene product Yrk (York), as an acronym for Yes-related kinase. As predicted from the cDNA sequence, the Yrk prote...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::Replication origins are 'licensed' for a single initiation event by loading Mcm2-7 complexes during late mitosis and G1. Licensing is blocked at other cell cycle stages by the activity of cyclin-dependent kinases and a small protein called geminin. Here, we describe the effects of over-expressing a non-degradable form...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205910
更新日期:2002-09-26 00:00:00
abstract::Human Papillomavirus (HPV) type 16 is the most frequently detected HPV in cervical cancer. Although epidemiologic and experimental evidence indicates a prominent role for HPV infection in the development of this disease, other factors are also involved. Altered expression of the ets family transcription factors erg an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201058
更新日期:1997-05-08 00:00:00
abstract::Cancer cells show deviant behavior that induces apoptotic signaling. To survive, cancer cells typically acquire changes enabling evasion of death signals. One way they do this is by increasing the expression of anti-apoptotic BCL-2 proteins. Anti-apoptotic BCL-2 family proteins antagonize death signaling by forming he...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2009.52
更新日期:2008-12-01 00:00:00
abstract::Senescence is an irreversible growth arrest phenotype adopted by cells that has a key role in protecting organisms from cancer. There is now considerable interest in therapeutic strategies that reactivate this process to control the growth of cancer cells. Protein kinase-Cι (PKCι) is a member of the atypical PKC famil...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.524
更新日期:2012-08-02 00:00:00
abstract::Resistance of pancreatic cancer to current treatments including radiotherapy remains a major challenge in oncology and may be caused by defects in apoptosis programs. Since 'inhibitor of apoptosis proteins' (IAPs) block apoptosis at the core of the apoptotic machinery by inhibiting caspases, therapeutic modulation of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210502
更新日期:2007-10-25 00:00:00
abstract::T-cell acute lymphoblastic leukemia (T-ALL) frequently involves aberrant expression of TAL1 (T-cell acute lymphocytic leukemia 1) and LMO2, oncogenic members of the TAL1 transcriptional complex. Transcriptional activity of the TAL1-complex is thought to have a pivotal role in the transformation of thymocytes and is as...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.481
更新日期:2016-08-04 00:00:00
abstract::Germ-line alterations in BRCA1 are associated with an increased susceptibility to breast and ovarian cancer. BRCA1 is a 220-kDa protein that contains a tandem of two BRCA1 C-Terminal (BRCT) domains. Among missense and nonsense BRCA1 mutations responsible for family breast cancer, some are located into the BRCT tandem ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205915
更新日期:2002-10-03 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease and a major health problem in the United States. While the cytokine TGF-β has been implicated in PDAC development, it can exert both pro-tumorigenic and anti-tumorigenic effects that are highly context dependent and incompletely understood. Using three-dimens...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0264-6
更新日期:2018-08-01 00:00:00
abstract::The p53 transcription factor has a critical role in cell stress response and in tumor suppression. Wild-type p53 protein is a growth modulator and its inactivation is a critical event in malignant transformation. It has been recently demonstrated that wild-type p53 has developmental and differentiation functions. Inde...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.31
更新日期:2011-07-07 00:00:00
abstract::Radicicol, an inhibitor of Src-family protein-tyrosine kinases, causes morphological reversion of v-src- and v-Ha-ras-transformed fibroblasts and arrest of the cell cycle at both the G1 and the G2 phases. Radicicol was found to inhibit the growth of several other oncogene-transformed cell lines and human carcinoma cel...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201443
更新日期:1997-11-20 00:00:00
abstract::The neu oncogene encodes a 185,000 dalton transmembrane glycoprotein, p185. The current study examined the effects of p185-specific monoclonal antibody administration on the tumorigenic growth of neu-transformed NIH3T3 cells implanted into nude mice. Treatment with anti-p185 monoclonal antibodies of the IgG1, IgG2a, I...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::bcl-XS, a member of the bcl-2 family, has been shown to induce and/or sensitize some cells to undergo programmed cell death, and to negate the anti-apoptotic activity of bcl-XL and bcl-2 by mechanisms which are still uncertain. To help understand these mechanisms we have established stable derivatives of the K12 rat c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202224
更新日期:1998-12-10 00:00:00
abstract::In an effort to understand the mechanisms governing the regulation of the mouse Ron receptor gene, a mouse genomic library was screened and overlapping clones coding for the Ron gene and flanking DNA were identified. Continuous DNA sequence was obtained for approximately 16.4 kilobases. The gene, from the initiator me...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201508
更新日期:1998-01-08 00:00:00
abstract::Targeting Bruton tyrosine kinase (BTK) by ibrutinib is an effective treatment for patients with relapsed/refractory mantle cell lymphoma (MCL). However, both primary and acquired resistance to ibrutinib have developed in a significant number of these patients. A combinatory strategy targeting multiple oncogenic pathwa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.155
更新日期:2016-12-01 00:00:00
abstract::The mouse mammary epithelial cell hierarchy contains both multipotent stem cell as well as lineage-limited duct and lobular progenitor cell functions. The latter-also termed parity-identified mammary epithelial cells (PI-MECs)-are marked by beta-galactosidase (β Gal) expression following pregnancy and involution in wh...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.215
更新日期:2012-01-05 00:00:00
abstract::A distinctive property of Hepatocyte Growth Factor (HGF) is its ability to induce differentiation of tubular structures from epithelial and endothelial cells (branching tubulogenesis). The HGF receptor directly activates PI3 kinase, Ras and STAT signalling pathways and phosphorylates the adaptator GRB2 Associated Bind...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203514
更新日期:2000-03-16 00:00:00
abstract::The c-fos proto-oncogene is found to be overexpressed at least 30-fold in SMS-SB, a pre-B leukemic cell line compared to other cell types. No gross alteration of the c-fos gene structure in SMS-SB cells can be detected by karyotypic or Southern analyses. C-fos in SMS-SB cells can still be induced by serum, TPA and the...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::Migration and invasion inhibitory protein (MIIP) is recently identified as an inhibitor in tumor development. However, the regulatory mechanism and biological contributions of MIIP in pancreatic cancer (PC) have been not elucidated. In this study, we demonstrated a negative feedback of MIIP and hypoxia-induced factor-...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-017-0082-2
更新日期:2018-03-01 00:00:00
abstract::The CD4 T-cell surface antigen and the lymphocyte-specific tyrosine-protein kinase p56lck form a stable noncovalent complex in CD4+ T-lymphocytes. In this report, we demonstrate that these two gene products can also associate when co-expressed in NIH3T3 fibroblasts, therefore implying that other lymphoid specific comp...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::The p53 oncosuppressor is strictly maintained in an inactive form under normal conditions, while it is post-translationally activated by a variety of stresses, enacting different protective biological functions. Since one critical issue in cancer gene therapy is tumor specificity, we asked whether the tight p53 regula...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207042
更新日期:2004-01-15 00:00:00
abstract::Murine radiation-induced acute myeloid leukaemia (AML) is characterized by loss of one copy of chromosome 2. Previously, we positioned the critical haematopoietic-specific transcription factor PU.1 within a minimally deleted region. We now report a high frequency (>65%) of missense mutation at codon 235 in the DNA-bin...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208422
更新日期:2005-05-19 00:00:00
abstract::Injection of the human neurotropic polyomavirus, JCV, into neonatal hamsters causes tumors of glial origin. Previously, a rapidly proliferating cell line, HJC-15, which expresses high levels of the viral T-antigen, had been established from JCV-induced hamster glial tumors. In our analyses of the mechanisms involved i...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-03-21 00:00:00
abstract::Germline mutations in the tumor suppressor BRCA1 predispose women to breast and ovarian cancers. Current evidence demonstrates that mutations in BRCA1 do not directly result in tumor formation, but instead cause genetic instability, subjecting cells to high risks of malignant transformation. In an animal model in whic...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203269
更新日期:2000-02-21 00:00:00
abstract::L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.176
更新日期:2013-03-21 00:00:00
abstract::The mechanisms by which the p53 tumour suppressor protein would, in vivo, co-ordinate the adaptive response to genotoxic stress is poorly understood. p53 has been shown to transactivate several genes that could be involved in two main cellular responses, growth arrest and apoptosis. To get further insight into the tis...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203366
更新日期:2000-02-03 00:00:00
abstract::The C3H/HeJ (C3H), A/J and BALB/cByJ (BALB) mouse strains are respectively resistant, sensitive and intermediate regarding the induction of lung tumors by urethane. The phenotypic difference between C3H and A/J is largely determined by the Pas1 (Pulmonary adenoma susceptibility 1) gene on chromosome 6, the A/J allele ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201357
更新日期:1997-10-09 00:00:00