Abstract：
:Heparanase (HPA) is an endoglucuronidase that can promote the shedding of associated cytokines in several types of tumors. However, little is known about what controls the expression of HPA or its role in gastric cancer. In this study, we report for the first time that HGF regulates HPA expression to promote gastric cancer metastasis. In this study, HGF and HPA were found to be significantly expressed in 58 gastric cancer patients. High expression of both HGF and HPA was positively associated with TNM stage, invasion depth and poor prognosis. In MKN74 cells, exogenous HGF significantly increased HPA expression at both the mRNA and protein levels. Further study revealed that HGF first activated PI3K/Akt signaling. NF-κB signaling was activated downstream of PI3K/Akt and promoted HPA expression. However, when c-met, PI3K/Akt or NF-κB signal inhibitors were used, HPA expression was significantly decreased. All of these results indicate that HGF regulates HPA expression by PI3K/Akt and downstream NF-κB signaling. Using bioinformatics and the ChIP assay, p65 was observed to bind to the HPA promoter. Furthermore, HGF significantly induced tumor cell migration, whereas treatment with an NF-κB inhibitor decreased migration. Moreover, when HPA was overexpressed in MKN74 cells, migration was significantly enhanced, and the HGF concentration was increased. However, when HPA was down-regulated in MKN45 cells, migration and HGF levels decreased. Together, these results demonstrate that HGF/c-met can activate PI3K/Akt and downstream NF-κB signaling to promote HPA expression and subsequent tumor metastasis.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Hao NB,Tang B,Wang GZ,Xie R,Hu CJ,Wang SM,Wu YY,Liu E,Xie X,Yang SMdoi
10.1016/j.canlet.2015.02.043subject
Has Abstractpub_date
2015-05-28 00:00:00pages
57-66issue
1eissn
0304-3835issn
1872-7980pii
S0304-3835(15)00158-5journal_volume
361pub_type
杂志文章相关文献
CANCER LETTERS文献大全abstract：:The notions of inter- and intra-tumour heterogeneity (ITH) have been recognised for many years but recent advances in sequencing technology are allowing the true extent of both forms of heterogeneity to be revealed in detail for the first time. In this review we examine the current evidence for ITH, the possibility of...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2012.10.031
更新日期：2013-11-01 00:00:00
abstract：:Cucurbitacin B is a natural anti-cancer compound found in Cucurbitaceae. Although the anti-cancer activity of cucurbitacin B in human leukemia cells has been reported, the underlining mechanism is still unclear. To clarify its anti-cancer activity and the mechanism of action, five different leukemia cell lines (CCRF-C...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2009.07.015
更新日期：2010-03-01 00:00:00
abstract：:A hepatic mixed-function oxygenase system gave enhanced biphenyl 2-hydroxylation in the presence of known carcinogens in vitro and was therefore suggested as a convenient short-term assay for the detection of potentially dangerous compounds. However, the test did not yield the expected increase of biphenyl 2-hydroxyla...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(79)80017-8
更新日期：1979-01-01 00:00:00
abstract：:Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural antioxidant found in plants, such as grapes, that studies suggest has cancer chemopreventive activity. We investigated the effects of resveratrol on DNA binding via esterification reactions with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(02)00061-7
更新日期：2002-08-08 00:00:00
abstract：:Bone metastasis is a major cause of prostate cancer (PCa) mortality. Although docetaxel chemotherapy initially extends patients' survival, in most cases PCa becomes chemoresistant and eventually progresses without a cure. In this study, we developed a novel small-molecule compound BKM1972, which exhibited potent in vi...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2019.01.010
更新日期：2019-04-01 00:00:00
abstract：:Classical Hodgkin lymphoma (cHL) tumor cells are surrounded by a protective tumor microenvironment (TME). Trabectedin, an anticancer drug targeting both tumor cells and TME, demonstrated a potent antitumor activity against Hodgkin Reed Sternberg (HRS) cells. It was cytotoxic against cHL cell lines, including the doxor...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2020.12.015
更新日期：2021-03-01 00:00:00
abstract：:We investigated the molecular effects of 3,4,2',4'-tetrahydroxychalcone (butein) treatment in two human hepatoma cancer cell lines-HepG2 and Hep3B. Butein treatment inhibited cancer cell growth by inducing G(2)/M phase arrest and apoptosis. Butein-induced G(2)/M phase arrest was associated with increased ATM, Chk1, an...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2009.07.002
更新日期：2010-02-28 00:00:00
abstract：:Breast cancer cells in their virulent undifferentiated state are characterized by lack of functional estrogen receptors (ER) and/or progesterone receptors (PR) as well as relatively low levels of other normal differentiation markers such as milk proteins and lipid droplets. To date, no method for in situ elevation of ...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(03)00146-0
更新日期：2003-05-08 00:00:00
abstract：:The mechanism of DDB (dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxy biphenyl-2,2'-dicarboxylate) prevention of aflatoxin B1 (AFB1)-induced hepatotoxicity in rats has been investigated. Pretreatment of DDB (200 mg/kg) daily for 4 days significantly suppressed (P < 0.05) the AFB1-induced hepatic damage as evidenced...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/0304-3835(95)03688-s
更新日期：1995-03-02 00:00:00
abstract：:Inhibition of DNA synthesis was observed and quantitated in hamster buccal pouch epithelium exposed in vivo and in vitro to indirect acting carcinogens. Topical application of a 0.5% solution of the potent hamster buccal pouch carcinogen 7,12-dimethylbenz[a]-anthracene (DMBA) acutely inhibited epithelial DNA synthesis...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/0304-3835(90)90210-o
更新日期：1990-09-01 00:00:00
abstract：:The limitations of current chemotherapies have motivated research in developing new treatments. Growing evidence shows that interaction between tumors and their microenvironment, but not tumor cells per se, is the key factor in tumor progression and therefore of obvious scientific interest and therapeutic value. Exoso...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2015.07.014
更新日期：2015-10-10 00:00:00
abstract：:BAT monoclonal antibody exhibited anti-tumor activity mediated by T and NK cells. We have evaluated the efficacy of murine and humanized BAT for the treatment of human colorectal carcinoma liver metastases in nude mice. HM7, a human colorectal carcinoma was injected into the spleen to colonize the liver. A single intr...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2005.06.046
更新日期：2005-11-18 00:00:00
abstract：:The carbohydrate epitope, alphaGal epitope, is known as a major xenoantigen. The epitope exists abundantly in non-primate mammals and has recently been found on C-type retroviruses. Humans and Old World monkeys have anti-alphaGal antibody, a natural antibody. The present study was performed to examine if the alphaGal ...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(01)00377-9
更新日期：2001-03-26 00:00:00
abstract：:Acute myeloid leukemia (AML) cells in vivo are constantly exposed to lymphangiogenic cytokines such as VEGF-C. However, it is poorly understood how the VEGF-C signaling modulates the immune functions in the tumor microenvironment. We have previously reported that natural killer (NK) cells in AML patients strongly upre...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2014.08.027
更新日期：2014-11-28 00:00:00
abstract：:Growing evidence from epidemiologic and preclinical studies suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of gastrointestinal (GI) cancers, including esophageal, gastric, pancreatic, colorectal cancer, and hepatocellular carcinoma. However, there is also evidence indicating the absence of...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2013.09.001
更新日期：2014-04-10 00:00:00
abstract：:NLRC5, the largest member of nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to regulate immune responses and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not yet been well demonstrate...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2016.03.006
更新日期：2016-06-28 00:00:00
abstract：:Although pectenotoxin-2 (PTX-2) is known to modify the actin cytoskeleton, very little is known about its apoptosis mechanism. In this study, we investigated whether PTX-2 induces apoptotic effects through suppression of the NF-kappaB signaling pathway in several leukemia cell types. PTX-2 significantly induced growth...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2008.05.034
更新日期：2008-11-18 00:00:00
abstract：:Patients with inadequate anti-cancer T cell responses experience limited benefit from immune checkpoint inhibitors and other immunotherapies that require T cells. Therefore, treatments that induce de novo anti-cancer T cell immunity are needed. One strategy - referred to as in situ vaccination - is to deliver chemothe...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2019.114427
更新日期：2019-09-10 00:00:00
abstract：:Estrogens are important for the development and growth of estrogen receptor (ER)-positive breast cancer, for which anti-estrogen therapy is one of the most effective treatments. However, its efficacy can be limited by either de novo or acquired resistance. Aromatase is a key enzyme for the biosynthesis of estrogens, a...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2014.05.003
更新日期：2014-08-28 00:00:00
abstract：:Genomic instability is characteristic of malignant cells, and a strong correlation exists between abnormal karyotype and tumorigenicity. Increased expression of the homologous recombination and DNA repair protein Rad51 has been reported in immortalized cell lines and multiple primary tumor cell types which could alter...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2004.08.009
更新日期：2005-02-10 00:00:00
abstract：:There is considerable direct evidence that calcium binding protein ANX A2 is a potential target for treating aggressive breast cancer. The most compelling data are based on the finding of ANX A2 overexpression in aggressive triple negative human breast cancer (TNBC) cell lines and in human breast cancer tissues. Previ...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2016.01.013
更新日期：2016-04-01 00:00:00
abstract：:Indomethacin is a non-steroidal anti-inflammatory agent that inhibits prostaglandin synthesis. Administration of indomethacin, in doses which were non-toxic to normal BALB/c mice, to mice bearing the BCL1 leukemia resulted in increased mortality of these animals. This effect was only observed if the indomethacin was a...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/0304-3835(84)90147-2
更新日期：1984-06-01 00:00:00
abstract：:Human epidermal growth factor receptor 2 (HER2) is an attractive target for cancer vaccine. However, autoimmune tolerance prevents vaccines based on HER2 protein from inducing long-lasting, highly effective anti-tumor immunity. In this study, we proved that the introduction of p-nitrophenylalanine in the universal T c...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2018.05.021
更新日期：2018-08-28 00:00:00
abstract：:Amplification and overexpression of PPM1D (protein phosphatase magnesium-dependent 1 delta) has been observed in various cancer cell lines and primary tumors and has also been associated with cancers of poor prognosis. In addition to the negative feedback regulation of p38-p53 signaling, PPM1D inhibits other tumor sup...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2007.09.019
更新日期：2008-01-18 00:00:00
abstract：:Arginine deiminase (ADI), isolated from Mycoplasma cell extracts, has been suggested to inhibit endothelial cell growth in vitro. However, anti-angiogenic activity by ADI has not yet been demonstrated. In this study, we investigated the in vitro effect of recombinant ADI (rADI) on the growth, migration, and tube forma...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(01)00793-5
更新日期：2002-09-26 00:00:00
abstract：:Effects of the green tea catechins (GTCs) on the late promotion or progression stage of mammary gland carcinogenesis were examined in female Sprague-Dawley (SD) rats pretreated with 7,12-dimethylbenz(a)anthracene (DMBA). A total of 84 7-week-old rats received a 50 mg/kg body weight intra-gastric dose of DMBA, and star...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/s0304-3835(96)04560-0
更新日期：1997-01-30 00:00:00
abstract：:Glioblastoma multiforme (GBM), a malignant brain tumor, is the deadliest form of human cancer with low survival rates because of its highly invasive nature. In recent years, there has been a growing appreciation for the role that glioblastoma stem cells (GSCs) play during tumorigenesis and tumor recurrence of GBM. GSC...
journal_title：Cancer letters
pub_type： 杂志文章,评审
doi：10.1016/j.canlet.2018.05.007
更新日期：2018-08-10 00:00:00
abstract：:Angiogenesis remains a sensible target for pancreatic ductal adenocarcinoma (PDAC) therapy. VEGF, PDGF, FGF and their receptors are expressed at high levels and correlate with poor prognosis in human PDAC. Nintedanib is a triple angiokinase inhibitor that targets VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β signaling. We invest...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2014.12.027
更新日期：2015-03-01 00:00:00
abstract：:Tumor angiogenesis has been found to be prognostically significant in many types of malignant tumors. We assessed tumor vascularity in 43 cases of histologically proven primary fallopian tube cancer, FIGO stage I-IV, using the highly specific endothelial cell marker CD34. Microvessel count was determined by counting C...
journal_title：Cancer letters
pub_type： 杂志文章,多中心研究
doi：10.1016/s0304-3835(99)00104-4
更新日期：1999-07-01 00:00:00
abstract：:Oesophageal cancer is associated with high morbidity and mortality rates because it is highly invasive and prone to recurrence and metastasis, with a five-year survival rate of <20%. Therefore, there is an urgent need for new methods aimed at improving therapeutic intervention. Several studies have shown that targeted...
journal_title：Cancer letters
pub_type： 杂志文章
doi：10.1016/j.canlet.2020.10.005
更新日期：2021-01-01 00:00:00
