共查询到20条相似文献,搜索用时 31 毫秒
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Binhui Xie Weihao Lin Junming Ye Xiaonong Wang Bing Zhang Shiqiu Xiong Heping Li Guosheng Tan 《Journal of experimental & clinical cancer research : CR》2015,34(1)
Background
Several studies have found that DDR2 is up-regulated in many tumor types and facilitates tumor progression. However, the role of DDR2 in hepatocellular carcinoma (HCC) progression and its downstream signaling pathways remain unclear.Methods
DDR2 expression was assessed in several cell lines and 112 pairs of HCC and matched adjacent noncancerous liver tissues. Clinical significance of DDR2 in HCC was analyzed. Phosphorylated DDR2 (p-DDR2) expression was detected by immunoblotting to evaluate its correlation with DDR2. The effect of DDR2 on HCC cell migration and invasion were examined. Cycloheximide chase experiments were performed to detect the half-life of SNAIL1. Moreover, DDR2 expression was detected by immunohistochemistry to evaluate its correlation with SNAIL1. The regulatory effect of DDR2 on ERK signaling, SNAIL1, EMT, MT1-MMP and MMP2 was confirmed by immunoblotting. The effect of type I collagen on DDR2/ERK2/SNAIL1 signaling was assessed.Results
DDR2 was more highly expressed in HCC than in non-HCC tissues. DDR2 overexpression was correlated with clinicopathological features of poor prognosis. Clinical analysis revealed that DDR2 is an independent prognostic marker for predicting overall survival and disease free survival of HCC patients. Overexpression of DDR2 is associated with p-DDR2 amplification. In vitro studies showed that DDR2 facilitates HCC cell invasion, migration and EMT via activating ERK2 and stabilizing SNAIL1. DDR2 can up-regulate MT1-MMP and MMP2 expression through ERK2/SNAIL1 signaling in HCC. Additionally, collagen I can induce DDR2/ERK2/SNAIL1 signaling activation in HCC cells.Conclusions
Our findings suggest that DDR2 plays an important role in promoting HCC cell invasion and migration, and may serve as a novel therapeutic target in HCC. 相似文献3.
Dawei Guo Xuezhong Hou Hongbin Zhang Wenyu Sun Lei Zhu Jian Liang Xiaofeng Jiang 《Journal of experimental & clinical cancer research : CR》2011,30(1):97
Background
Brain-derived neurotrophic factor (BDNF) and its receptor Tropomysin-related kinase B (TrkB) are commonly up-regulated in a variety of human tumors. However, the roles of BDNF/TrkB in hepatocellular carcinoma (HCC) have been poorly investigated.Methods
We evaluated the expressions of BDNF and TrkB in 65 cases of HCC by immunohistochemical staining. Moreover, in human HCC cell lines of HepG2 and high metastatic HCCLM3, the secretory BDNF in supernatant was measured by ELISA, the effects of BDNF neutralizing antibody or Trk tyrosine kinase inhibitor K252a on apoptosis and invasion were examined by flow cytometry and transwell assay respectively.Results
Higher expression of BDNF (63.1%) or positive expression of TrkB (55.4%) was found in HCC specimens, which was significantly correlated with multiple and advanced stage of HCC. BDNF secretory level in HCCLM3 was higher than that in HepG2 cells. Both anti-BDNF and K252a effectively induced apoptosis and suppressed invasion of HepG2 and HCCLM3 cells.Conclusions
These findings suggested that BDNF/TrkB are essential for HCC cells survival and invasion. BDNF/TrkB signaling should probably be an effective target to prevent HCC advancement. 相似文献4.
N Akanuma I Hoshino Y Akutsu K Murakami Y Isozaki T Maruyama G Yusup W Qin T Toyozumi M Takahashi H Suito X Hu N Sekino H Matsubara 《British journal of cancer》2014,110(1):189-198
Background:
FSCN1 and matrix metalloproteinase 14 (MMP14) are both invadopodia-related proteins. We herein elucidate the tumourigenicity of these proteins and identify novel therapeutic agents in esophageal squamous cell carcinoma (ESCC).Methods:
FSCN1 and MMP14 were evaluated by immunohistochemistry and quantitative PCR, and microRNA (miR)-133a was also evaluated by PCR in surgical ESCC specimens. The roles of FSCN1, MMP14 and miR-133a were established in ESCC cells.Results:
The expression of FSCN1 or MMP14 was an independent poor prognostic factor according to a multivariate analysis of immunohistochemistry, and their co-expression correlated with the poorest overall survival (OS) out of all the examined factors. Additionally, their mRNAs significantly correlated and both inversely correlated with miR-133a in surgical specimens. Transfection of a miR-133a mimic decreased the mRNA and protein levels of both FSCN1 and MMP14 in ESCC cells. The knockdown of FSCN1 or MMP14 and transfection of a miR-133a mimic inhibited the proliferation and invasion of ESCC cells. Patients with a lower miR-133a expression have a significantly poorer OS than those with a higher expression.Conclusion:
The combined expression of FSCN1 and MMP14 is associated with a poor prognosis, and miR-133a, which regulates their mRNAs, can serve as a strong tumour suppressor of ESCC. 相似文献5.
A Tsuru T Setoguchi Y Matsunoshita H Nagao-Kitamoto S Nagano M Yokouchi S Maeda Y Ishidou T Yamamoto S Komiya 《British journal of cancer》2015,112(7):1232-1240
Background:
Activation of the Notch pathway has been reported in various types of cancers. However, the role of the hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) in osteosarcoma is unknown. We examined the function of HEY1 in osteosarcoma.Methods:
Expression of HEY1 was studied in human osteosarcoma. The effects of HEY1 in osteosarcoma were evaluated in vitro and in a xenograft model. Moreover, we examined the function of matrix metallopeptidase 9 (MMP9) as a downstream effector of HEY1.Results:
HEY1 was upregulated in human osteosarcoma. Knockdown of HEY1 inhibited the invasion of osteosarcoma cell lines. In contrast, the forced expression of HEY1 increased the invasion of mesenchymal stem cell. In addition, lung metastases were significantly inhibited by the knockdown of HEY1. We found that MMP9 was a downstream effector of HEY1 that promotes the invasion of osteosarcoma cells. Knockdown of HEY1 decreased the expression of MMP9. Addition of MMP9 rescued the invasion of osteosarcoma cells that had been rendered less invasive by knockdown of HEY1 expression.Conclusions:
Our findings suggested that HEY1 augmented the metastasis of osteosarcoma via upregulation of MMP9 expression. Therefore, inhibition of HEY1 may be a novel therapeutic strategy for preventing osteosarcoma metastasis. 相似文献6.
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Bo Zhou Hongxu Chen Dong Wei Yi Kuang Xiaobiao Zhao Guangyao Li Jun Xie Ping Chen 《Journal of experimental & clinical cancer research : CR》2014,33(1):55
Background
To understand the involvement of structural maintenance of chromosome 4 (SMC4) in the development and progression of hepatocellular carcinoma (HCC).Methods
Real-time quantitative PCR and Western Blotting were applied to measure the expression of SMC4 in HCC samples and cell lines. The tumor-promoting effect of SMC4 was determined by WST-1, soft agar colony formation, cell motility and invasion assays. The SMC4 target signal pathway was identified by luciferase reporter and real-time quantitative PCR assays.Results
The upregulation of SMC4 was frequently detected in HCC samples and cell lines. Functional assays demonstrated that SMC4 could effectively promote tumor cell growth rate, colony formation in soft agar, wound-healing and invasion. Further studies showed that increased miR-219 levels caused a significant decrease in the SMC4 expression, and SMC4 inhibitor downregulated JAK2/Stat3 expression at both the mRNA and protein levels.Conclusions
Our findings provide new insight into SMC4 function and the mechanisms of growth and invasion of HCC. 相似文献10.
Zhe Bao Wu Lin Cai Shao Jian Lin Zhen Kun Xiong Jiang Long Lu Ying Mao Yu Yao Liang Fu Zhou 《Neuro-oncology》2013,15(9):1264-1275
Background
The expression profile of high-mobility group box 2 (HMGB2) in patients with glioblastoma multiforme (GBM) and its clinical signature with underlying mechanisms were not fully explored.Methods
HMGB2 protein levels were measured in 51 GBM patients by immunohistochemical studies. To clarify the precise role of HMGB2 on cell invasion and viability of 3 GBM cell lines, we did in vitro and in vivo analyses with lentivirus vectors and small interfering RNA. Transwell invasion assays and wound-healing assays were used to analyze the invasion of GBM cells. Expression of p53 and matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot.Results
HMGB2 protein expression was significantly higher in GBM than in controlled brain tissues (P < .0001). HMGB2 overexpression was significantly correlated with shorter overall survival time, which was the only independent prognostic factor for overall survival in a multivariate analysis (P = .017). HMGB2 knockdown by small interfering RNA decreased cell viability and invasion in vitro and significantly decreased tumor volume in vivo, which might be involved in the change of p53 expression and the balance of MMP2/TIMP2. Moreover, silencing of HMGB2 could significantly increase the sensitivity of GBM cells to temozolomide chemotherapy.Conclusions
Our present data suggest that HMGB2 expression is a significant prognostic factor and might play an important role in cell invasion and temozolomide-induced chemotherapeutic sensitivity of GBM. This study highlights the importance of HMGB2 as a novel prognostic marker and an attractive therapeutic target of GBM. 相似文献11.
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Ming-Qi Fan Chi-Bing Huang Yan Gu Ya Xiao Jin-Xin Sheng Lin Zhong 《Journal of experimental & clinical cancer research : CR》2013,32(1):21
Background
Growing evidences indicate microRNAs play important roles in cancer development, progression, metastasis and may constitute robust biomarkers for cancer prognosis. The aim of this study was to identify the clinical and functional association of microRNA-20a (miR-20a) in hepatocellular carcinoma (HCC).Methods
MiR-20a was detected using Taqman real-time polymerase chain reaction. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-20a with survival of patients. The potential functions of miR-20a on proliferation were evaluated by proliferation and flow cytometry analysis. The direct target gene of miR-20a was also identified by luciferase reporter assays.Results
MiR-20a was lower in primary HCC than normal liver, and were further decreased in those with post-liver transplantation (LT) HCC recurrence compared with those with non-recurrence (p = 0.001). Patients with lower miR-20a expression had significantly poorer recurrence-free survival (RFS, Log rank p < 0.001) and overall survival (OS, Log rank p < 0.001). Multivariate analysis revealed that lower miR-20a was an independent predictor of poor prognosis. MiR-20a restoration could suppress HepG2 and SMMC-7721 cells proliferation and induce cell cycle G1 arrest and apoptosis. Subsequent investigations revealed that miR-20a directly targeted myeloid cell leukemia sequence 1 (Mcl-1) and reduced the endogenous protein level of Mcl-1 in HCC cells.Conclusions
MiR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Down-regulation of miR-20a increases the proliferation abilities of HCC cells. Our findings suggest miR-20a may represent a novel potential therapeutic target and biomarker for survival of HCC patients. 相似文献13.
Zijie Liu Kang Ling Xia Wu Ju Cao Bin Liu Suyan Li Qiong Si Yan Cai Chen Yan Yan Zhang Yaguang Weng 《Journal of experimental & clinical cancer research : CR》2009,28(1):156
Background
CENP-E, one of spindle checkpoint proteins, plays a crucial role in the function of spindle checkpoint. Once CENP-E expression was interrupted, the chromosomes can not separate procedurally, and may result in aneuploidy which is a hallmark of most solid cancers, such as hepatocellular carcinoma (HCC). We investigate the expression of CENP-E in human hepatocellular carcinoma,. and analyze the effect of low CENP-E expression on chromosome separation in normal liver cell line (LO2).Methods
We determined its levels in HCC and para-cancerous tissues, human hepatocellular carcinoma-derived cell line (HepG2) and LO2 cell line using real time quantitative PCR (QPCR) and Western blot. Further to know whether reduction in CENP-E expression impairs chromosomes separation in LO2 cells. we knocked down CENP-E using shRNA expressing vector and then count the aneuploid in LO2 cells using chromosomal counts assay.Results
We found that both CENP-E mRNA and protein levels were significantly reduced in HCC tissues and HepG2 cells compared with para-cancerous tissues and LO2 cells, respectively. A significantly-increased proportion of aneuploid in these down-knocked LO2 cells compared with those treated with control shRNA vector.Conclusions
Together with other results, these results reveal that CENP-E expression was reduced in human HCC tissue, and low CENP-E expression result in aneuploidy in LO2 cells. 相似文献14.
Ai-Rong Qian Wei Zhang Jian-Ping Cao Peng-Fei Yang Xiang Gao Zhe Wang Hui-Yun Xu Yuan-Yuan Weng Peng Shang 《Journal of experimental & clinical cancer research : CR》2008,27(1):1-14
Background
CD147 plays a critical role in the invasive and metastatic activity of hepatocellular carcinoma (HCC) cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases (MMPs). Tumor cells adhesion to extracellular matrix (ECM) proteins is the first step to the tumor metastasis. MMPs degrade the ECM to promote tumor metastasis. The aim of this study is to investigate the effects of small interfering RNA (siRNA) against CD147 (si-CD147) on hepatocellular carcinoma cells' (SMMC-7721) architecture and functions.Methods
Flow cytometry and western blot assays were employed to detect the transfection efficiency of si-CD147. Confocal microscopy was used to determine the effects of si-CD147 on SMMC-7721 cells' cytoskeleton. Invasion assay, gelatin zymography and cell adhesion assay were employed to investigate the effects of si-CD147 on SMMC-7721 cells' invasion, gelatinase production and cell adhesive abilities. Western blot assay was utilized to detect the effects of si-CD147 on focal adhesion kinase (FAK), vinculiln and mitogen-activated protein kinase (MAPK) expression in SMMC-7721 cells.Results
Downregulation of CD147 gene induced the alteration of SMMC-7721 cell cytoskeleton including actin, microtubule and vimentin filaments, and inhibited gelatinase production and expression, cells invasion, FAK and vinculin expression. si-CD147 also blocked SMMC-7721 cells adhesion to collagen IV and phosphorylation level of SAPK/JNKs. SAPK/JNKs inhibitor SP600125 inhibited gelatinase production and expression.Conclusion
CD147 is required for normal tumor cell architecture and cell invasion. Downregulation of CD147 affects HCC cell structure and function. Moreover, the alteration of cell behavior may be related to SAPK/JNK Pathway. siRNA against CD147 may be a possible new approach for HCC gene therapy. 相似文献15.
Xianfan Ding Dong-Rong Yang Liqun Xia Bide Chen Shicheng Yu Yuanjie Niu Mingchao Wang Gonghui Li Chawnshang Chang 《Molecular cancer》2015,14(1)
Background
TR4 nuclear receptor 4 (TR4) plays an important role in macrophages-associated foam cell formation of cardiovascular diseases and infiltrating macrophages are critical for prostate cancer (PCa) progression. However, the linkage of macrophages and TR4 and their impacts on PCa metastasis remains unclear.Results
Knocking-down TR4 in human PCa cells (C4-2, CWR22Rv1), but not in human macrophages cells (THP-1), led to suppress the macrophages infiltration to PCa cells. The consequences of such suppression of the recruitment of macrophages toward PCa then resulted in suppressing the PCa cell invasion. Mechanism dissection found that knocking-down TR4 in PCa cells suppressed metastasis-related genes including MMP2, with induction of TIMP-1. Interruption assays using TIMP-1 neutralizing antibody could then reverse TR4-macrophage-mediated PCa invasion. IHC staining showed higher TR4 level, more macrophage infiltration, lower TIMP-1 and stronger MMP2/MMP9 in tumor tissues of the Gleason score 5 + 4 patients compared with the Gleason score 3 + 3 patients.Conclusion
Targeting TR4 in prostate tumor microenvironment might represent a potential new therapeutic approach to better battle PCa metastasis.Electronic supplementary material
The online version of this article (doi:10.1186/s12943-014-0281-1) contains supplementary material, which is available to authorized users. 相似文献16.
目的探讨微小RNA(mi RNA)-574-5p通过靶基因哺乳动物高温需求因子A1(HTRA1)调控肝癌细胞增殖、侵袭、迁移的分子机制。方法采用实时荧光定量聚合酶链反应(q RT-PCR)、蛋白质印迹法(Western blot)检测正常细胞株L02及肝癌细胞株Hep G2、SMMC-7721、BEL-7402中mi RNA-574-5p、HTRA1的表达水平,采用Western blot检测转染后Hep G2细胞中细胞周期蛋白D1(cyclin D1)、p21、p27、基质金属蛋白酶(MMP)2、MMP9、MMP14蛋白的表达水平,采用噻唑蓝(MTT)法检测细胞增殖情况,采用Transwell实验检测细胞迁移和侵袭能力,采用双荧光素酶实验检测mi RNA-574-5p对HTRA1活性的影响。结果与L02细胞系比较,肝癌细胞系Hep G2、SMMC-7721、BEL-7402中mi RNA-574-5p的表达水平均升高,HTRA1 m RNA和HTRA1蛋白的表达水平均下降(P﹤0.05)。anti-mi RNA-574-5p组Hep G2细胞中mi RNA-574-5p的表达水平明显低于anti-mi RNA-NC组(P﹤0.01)。与anti-mi RNA-NC组比较,anti-mi RNA-574-5p组Hep G2细胞48、72 h的增殖率及cyclin D1、MMP2、MMP9、MMP14蛋白的表达水平均明显降低,迁移、侵袭数目均明显减少,p21、p27蛋白的表达水平均明显升高(P﹤0.01)。pc DNA-HTRA1组Hep G2细胞中HTRA1蛋白的表达水平明显高于pc DNA组(P﹤0.01)。与pc DNA组比较,pc DNA-HTRA1组Hep G2细胞48、72 h的增殖率及cyclin D1、MMP2、MMP9蛋白的表达水平均明显降低,p21蛋白的表达水平明显升高,迁移、侵袭数目均明显减少(P﹤0.01)。双荧光素酶报告实验显示,mi RNA-574-5p+WT-HTRA1组Hep G-2细胞的荧光素酶活性明显低于mi RNA-NC+WT-HTRA1组(P﹤0.01)。mi RNA-574-5p+MUT-HTRA1组Hep G-2细胞的荧光素酶活性与mi RNA-NC+MUT-HTRA1组比较,差异无统计学意义(P﹥0.05)。与anti-mi RNA-574-5p+si-NC组比较,anti-mi RNA-574-5p+si-HTRA1组Hep G2细胞中HTRA1蛋白的表达水平降低,培养48、72 h的肝癌Hep G2细胞的增殖率均升高,cyclin D1、MMP2、MMP9蛋白的表达水平均升高,细胞迁移、侵袭数目均增多,p21蛋白的表达水平降低(P﹤0.05)。结论mi RNA-574-5p通过靶向负调控HTRA1基因调控肝癌细胞的增殖、侵袭、迁移。 相似文献
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Paquette B Therriault H Desmarais G Wagner R Royer R Bujold R 《British journal of cancer》2011,105(4):534-541
Background:
Recent evidences support that radiation can promote the invasion of cancer cells. As interactions between cancer cells and surrounding stromal cells can have an important role in tumour progression, we determined whether an irradiation to fibroblasts can enhance the invasiveness of breast cancer cells. The role of cyclooxygenase-2 (COX-2), an inflammatory enzyme frequently induced by radiotherapy, was investigated.Methods:
Irradiated 3T3 fibroblasts were plated in the lower compartment of invasion chambers and used as chemoattractant for non-irradiated human breast cancer cell MDA-MB-231, which are oestrogen receptor negative (ER(−)) and the oestrogen receptor positive (ER(+)) MCF-7 cells. Stimulation of COX-2 expression in irradiated 3T3 cells was measured by a semi-quantitative qPCR and western blot. Capacity of the major product of COX-2, the prostaglandin E2 (PGE2), to stimulate the production of the matrix metalloproteinase-2 (MMP-2) and cancer cell invasion were assessed with a zymography gel and invasion chambers.Results:
Irradiation (5 Gy) of 3T3 fibroblasts increased COX-2 expression and enhanced by 5.8-fold the invasiveness of non-irradiated MDA-MB-231 cells, while their migration was not modified. Addition of the COX-2 inhibitor NS-398 completely prevented radiation-enhancement of cancer cell invasion. Further supporting the potential role of COX-2, addition of PGE2 has increased cancer cell invasion and release of MMP-2 from the MDA-MB-231 cells. This effect of radiation was dependant on the expression of membrane type 1 (MT1)–MMP, which is required to activate the MMP-2, but was not associated with the ER status. Although irradiated fibroblasts stimulated the invasiveness of MDA-MB-231 ER(−) cells, no enhancement was measured with the ER(+) cell line MCF-7.Conclusions:
Radiation-enhancement of breast cancer cell invasion induced by irradiated 3T3 fibroblasts is not dependant on the ER status, but rather the expression of MT1–MMP. This adverse effect of radiation can be prevented by a specific COX-2 inhibitor. 相似文献20.
Shuhong Zhang Jianfeng Li Ying Jiang Yijun Xu Chengyong Qin 《Journal of experimental & clinical cancer research : CR》2009,28(1):71