Abstract：
BACKGROUND:Focal adhesion kinase (FAK) is overexpressed in a variety of cancers, such as breast, colon, prostate, ovary, and lung cancers. However, the mechanism by which extracellular matrix fibronectin stimulates lung cancer cell migration and invasion through FAK remains to be investigated. METHODS:The signalling pathways in fibronectin-mediated lung cancer cell migration and invasion were examined using western blotting. The metastasis function was detected by wound healing, migration and invasion assays. Further, RNA interference and kinase inhibitors were also used to study the downstream signals. RESULTS:In this study, we examined the FAK signalling pathways in relation to calpain-2 and RhoA in fibronectin-mediated lung cancer cell migration and invasion. We found that A549 lung epithelial cells stimulated by fibronectin showed increased phosphorylation of FAK and its downstream targets, Src, ERK1/2, phosphatidylinositol 3'-kinase (PI3K), and Akt. Consistent with this observation, depletion of FAK by siRNA resulted in the inhibition of Src, ERK1/2, PI3K, and Akt activity. In addition, the Src inhibitor, PP2, blocked the phosphorylation of FAK, ERK1/2, PI3K, and Akt. Conversely, inhibition of MEK1/2 using PD98059 reduced the expression of matrix metalloproteinase-9 (MMP9) and calpain-2. The PI3K inhibitor, LY294002, further blocked the expression of MMP9 and RhoA. Inhibition of both MEK1/2 and PI3K caused reduced cell migration and invasion. CONCLUSION:Our data suggest that fibronectin-mediated activation of FAK that leads to lung cancer metastasis could occur through ERK or PI3K/Akt regulation of MMP9/calpain-2 or MMP9/RhoA activity, respectively.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Meng XN,Jin Y,Yu Y,Bai J,Liu GY,Zhu J,Zhao YZ,Wang Z,Chen F,Lee KY,Fu SBdoi
10.1038/sj.bjc.6605154subject
Has Abstractpub_date
2009-07-21 00:00:00pages
327-34issue
2eissn
0007-0920issn
1532-1827pii
6605154journal_volume
101pub_type
杂志文章abstract：BACKGROUND:To estimate the accuracy of one-step nucleic acid amplification (OSNA) assay as an intra-operative sentinel lymph node biopsy (SLNB) for sentinel lymph node (SLN) metastasis in breast cancer. METHODS:PubMed, Cochrane Library and Web of Science databases were searched by two independent reviewers to retrieve...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析
doi：10.1038/bjc.2017.262
更新日期：2017-10-10 00:00:00
abstract：:Seventy-one patients suffering from acute myeloid leukaemia (AML) who were already in complete remission and had already received one further course of cytotoxic drugs as consolidation therapy were randomised to receive maintenance chemotherapy alone or the same maintenance chemotherapy plus immunotherapy with BCG and...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/bjc.1978.1
更新日期：1978-01-01 00:00:00
abstract：:Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined th...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603028
更新日期：2006-03-27 00:00:00
abstract：BACKGROUND:The urokinase plasminogen activator (uPA) system is one of the best-investigated protease systems, both under physiological and pathological conditions, including various types of cancer. However, effects of co-expression of members of the uPA system in soft-tissue sarcoma (STS) patients at the protein level...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605520
更新日期：2010-02-16 00:00:00
abstract：:More women are living with and surviving breast cancer, because of improvements in breast cancer care. Trastuzumab (Herceptin) has significantly improved outcomes for women with HER2-positive tumours. Concerns about the cardiac effects of trastuzumab (which fundamentally differ from the permanent myocyte loss associat...
journal_title：British journal of cancer
pub_type： 杂志文章,实务指引
doi：10.1038/sj.bjc.6604909
更新日期：2009-03-10 00:00:00
abstract：:Anti-vascular effects of the novel Vinca alkaloid, vinflunine have been investigated in the MAC 15A transplantable murine colon adenocarcinoma model and compared with those induced by the most recently identified clinically useful third generation Vinca. Administration of the maximum tolerated dose of either vinflunin...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1587
更新日期：2001-01-01 00:00:00
abstract：BACKGROUND:Gram-negative bacteria mediated gemcitabine resistance in pre-clinical models. We determined if intratumoural lipopolysaccharide (LPS) detection by immunohistochemistry is associated with outcome in advanced pancreatic ductal adenocarcinoma (PDAC) treated with gemcitabine and non-gemcitabine containing 1st-l...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-01029-7
更新日期：2020-10-01 00:00:00
abstract：:Hyper-activation of mitogen-activated protein kinase (MAPK) has recently been reported in several human cancers and activation of MAPK in those cancers may be associated with carcinogenesis through aberrant cell proliferation. To understand the roles of the MAPK pathway in colorectal tumorigenesis, we examined the sta...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690817
更新日期：1999-12-01 00:00:00
abstract：:Mice transplanted with NC carcinoma were treated with the thromboxane synthetase inhibitor dazmegrel (UK38485) or with nafazatrom (BAY G 6575), a compound that is reported to increase prostacyclin formation. Some experiments included the cytotoxic drugs methotrexate and melphalan. The tumours were excised under anaest...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.171
更新日期：1986-08-01 00:00:00
abstract：BACKGROUND:Breast cancer 1, early onset (BRCA1) is a tumour-suppressor gene associated with familial epithelial ovarian cancer (EOC). Reduced BRCA1 expression is associated with enhanced sensitivity to platinum-based chemotherapy. We sought to examine the prognostic relevance of BRCA1 expression in EOC patients treated...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1038/bjc.2013.70
更新日期：2013-04-02 00:00:00
abstract：:Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic signifi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602593
更新日期：2005-05-23 00:00:00
abstract：:No numerical aberration of chromosomes that might be specific for prostate cancer has so far been established. We used fluorescence in situ hybridisation (FISH) with centromere-specific probes for chromosomes 7, 8, 17, X and Y to establish the distribution of centromere copy numbers in frozen-stored or freshly prepare...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.617
更新日期：1996-12-01 00:00:00
abstract：:In advanced pancreatic cancer, level one evidence has established a significant survival advantage with chemotherapy, compared to best supportive care. The treatment-associated toxicity needs to be evaluated. This study examines the secondary outcome measures for chemotherapy in advanced pancreatic cancer using meta-a...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析
doi：10.1038/sj.bjc.6604436
更新日期：2008-07-08 00:00:00
abstract：:Hepatic arterial floxuridine (HAI) in 35 patients with systemic fluorouracil/folinic acid-resistant colorectal liver metastases achieved a 14% partial response and 26% disease stabilization rate, with a median response duration of 7 months from onset of HAI. ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1998.627
更新日期：1998-10-01 00:00:00
abstract：:The effect of the synthetic progesterone, megestrol acetate, on weight loss induced by both tumour necrosis factor alpha (TNF) as a model for the cachexia accompanying the acquired immunodeficiency syndrome and by a cachexia-inducing tumour (MAC16) has been studied in NMRI mice. Megestrol acetate was effective in prev...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.310
更新日期：1990-09-01 00:00:00
abstract：:A study was conducted on the effects of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on peroxisomal enzyme activities in mouse embryo fibroblasts C3H/10T1/2 C18 cells and chemically transformed C3H/10T1/2 MCA16 cells. TPA is a potent tumour promoter and treatment with this compound of the two cell lines induced peroxis...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.17
更新日期：1986-01-01 00:00:00
abstract：:Specimens from 45 patients with previously-untreated non-small cell lung cancer (NSCLC) were tested for in vitro chemosensitivity to ten drugs utilising the DiSC assay, which measures cell kill in the total (largely non-dividing) tumour cell population. Thirty-five assays were successful and 25 patients with advanced ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.5
更新日期：1992-01-01 00:00:00
abstract：:PEP005 is a novel ingenol angelate that modulates protein kinases C (PKC) functions by activating PKC delta and inhibiting PKC alpha. This study assessed the antiproliferative effects of PEP005 alone and in combination with several other anticancer agents in a panel of 10 human cancer cell lines characterised for expr...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604642
更新日期：2008-12-02 00:00:00
abstract：BACKGROUND:Cancer/testis-antigens (CTAs) are specifically expressed in human malignancies and testis tissue, but their molecular functions are poorly understood. CTAs serve as regulators of gene expression, cell cycle and spermatogenesis, as well as targets for immune-based therapies. The CTA PRAME is expressed in vari...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.187
更新日期：2016-08-09 00:00:00
abstract：BACKGROUND:Systemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.631
更新日期：2015-02-03 00:00:00
abstract：:The ability of human tumour cells to form colonies in soft agar is enhanced by the presence of autologous phagocytic/adherent cells. We investigated the effect of irradiation on the ability of the adherent cells to support human tumour colony formation. Relatively low doses of irradiation significantly increased the g...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1983.249
更新日期：1983-11-01 00:00:00
abstract：:Helicobacter has been suggested to play a possible role in hepatitis, gallstones, and hepatobiliary tumours. We assessed whether seropositivity to 15 H. pylori proteins was associated with subsequent incidence of 74 biliary tract and 105 liver cancer cases vs. 357 matched controls in the Prostate, Lung, Colorectal, an...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0961-0
更新日期：2020-09-01 00:00:00
abstract：:Recent studies involving animal models of cancer and clinicopathological analyses of human tumours suggest that the growth of lymphatic vessels (lymphangiogenesis) in or nearby tumours is associated with the metastatic spread of cancer. The best validated molecular signalling system for tumour lymphangiogenesis involv...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6603120
更新日期：2006-05-22 00:00:00
abstract：BACKGROUND:Most studies use hospital data to calculate postoperative complication rates (PCRs). We report on improving PCR estimates through use of patient-reporting. METHODS:A prospective cohort study of major surgery performed at 10 UK gynaecological cancer centres was undertaken. Hospitals entered the data contempo...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/bjc.2013.366
更新日期：2013-08-06 00:00:00
abstract：:The association between Ki-ras mutations and proliferation activity was investigated in a comprehensive series of biliary tract carcinomas (BTCs). We precisely microdissected samples of tissue from paraffin-embedded sections of 77 BTCs including 22 intrahepatic cholangiocarcinomas (ICCs), 36 extrahepatic cholangiocarc...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.459
更新日期：1996-09-01 00:00:00
abstract：:The level of expression of the multidrug resistance-associated protein (MRP1) in a panel of human ovarian carcinoma cell lines and their variants with acquired cisplatin resistance was determined using Western blotting. No overexpression of MRP1 was detected in any of the cell lines. In addition, we have transfected t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.461
更新日期：1998-07-01 00:00:00
abstract：BACKGROUND:Kaposi's Sarcoma Herpesvirus (KSHV) is a gammaherpesvirus strongly linked to human cancer. The virus is also able to induce immune suppression, effect that contributes to onset/progression of the viral-associated malignancies. As KSHV may infect macrophages and these cells abundantly infiltrate Kaposi's sarc...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0872-0
更新日期：2020-07-01 00:00:00
abstract：:The discoidin domain receptors, (DDR)1 and DDR2, have been linked to numerous human cancers. We sought to determine expression levels of DDRs in human lung cancer, investigate prognostic determinates, and determine the prevalence of recently reported mutations in these receptor tyrosine kinases. Tumour samples from 14...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603614
更新日期：2007-03-12 00:00:00
abstract：:To improve our understanding of the relationship and possible associations between human papillomavirus (HPV) infection and the development of cervical malignancies, the presence of multiple types of HPV DNA sequences in cervical carcinoma was determined in Chinese citizens living in two different geographical locatio...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.375
更新日期：1994-10-01 00:00:00
abstract：:The present study was designed to examine whether different p53 haplotypes of exon 4-intron 3-intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly high...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602271
更新日期：2005-01-17 00:00:00
