A novel angiogenesis inhibitor impairs lovo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation

Zhang, Y M; Dai, Bingling; Zheng, Lei; Zhan, Ying; Zhang, J; Smith, Wanli W.; Wang, X L; Chen, Y N; He, Langchong

doi:10.1038/cddis.2012.145

Cited by 35 publications

(23 citation statements)

References 43 publications

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“…They were stated as Breact with,^Bin same component,^and Bstate change.^And the cutpoint of state change was set as 12 % (Fig. 3) [19]. The study of ITGA2B and ITGA8 gene cluster indicated that in univariate Cox regression model, PIK3CA, SOS1, VWF, PIK3R1, Table 5).…”

Section: Resultsmentioning

confidence: 99%

ITGA2B and ITGA8 are predictive of prognosis in clear cell renal cell carcinoma patients

et al. 2015

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Integrins play an important role in cancer growth and metastasis. This study aimed at determining the predictive ability of integrins and associated genes identified through molecular network in clear cell renal cell carcinoma. A total of 525 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of integrins and related genes were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor size, tumor node metastasis (TNM), tumor grade, stage, laterality, and overall survival were collected. Cox proportional hazards regression model as well as Kaplan-Meier curve were used to assess the relative factors. Genes of integrin family that showed certain correlations with overall survival (OS) were further validated in the Fudan University Shanghai Cancer Center (FUSCC) cohort. In the TCGA cohort, after Cox proportional hazards analysis, ITGA2B (hazards ratio (HR) = 1.232, 95 % CI 1.097 to 1.383) and ITGA8 (HR = 0.804, 95 % CI 0.696 to 0.930) were shown predictive of ccRCC prognosis. Low ITGA8 expression was associated with poor prognosis for OS (log-rank test, p < 0.0001), while high level of ITGA2B expression was correlated with poor prognosis for OS (log-rank test, p < 0.0001). This finding was validated in FUSCC cohort (log-rank test, all p < 0.05). As a result, low ITGA8 expression was associated with poor prognosis for OS (log-rank test, p = 0.0053), while high level of ITGA2B expression was correlated with poor prognosis for OS (log-rank test, p < 0.0001). Plus, low ITGA8 expression was associated with poor prognosis for disease-free survival (DFS) in the TCGA cohort (log-rank test, p < 0.0001). In the gene cluster network analysis, GIT1 and SHC1 associated with ITGA2B and ITGA8 were identified as independent predictive factors of overall survival of ccRCC. ITGA2B, ITGA8, GIT1, and SHC1 were identified as independent prognostic factors of overall survival of ccRCC. This method may act as a tool to reveal more prognostic-associated genes in ccRCC.

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Section: Resultsmentioning

confidence: 99%

ITGA2B and ITGA8 are predictive of prognosis in clear cell renal cell carcinoma patients

et al. 2015

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“…Western blot bands demonstrated a decrease in phosphorylation of VEGFR‐2 after treatment with SiO 2 @LDH‐VP16 on A549 cells. There have been studies showing that suppression the phosphorylation of VEGFR‐2 led to inhibition of cancer cell migration and metastasis 47, 48. The prosurvival activity of phosphoinositide 3 kinase (PI3K)/Akt pathway has been identified that actively engages with the migratory process in motile cells, including metastatic cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Anti‐Metastatic and Anti‐Angiogenic Activities of Core–Shell SiO₂@LDH Loaded with Etoposide in Non‐Small Cell Lung Cancer

Zhu

Wang

et al. 2016

Advanced Science

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Currently, nanoparticles have gained a great attention in the anti‐tumor research area. However, to date, studies on the anti‐metastasis action of core–shell SiO2@LDH (LDH: layered double hydroxide) nanoparticles remain untouched. Two emerging aspects considered are establishing research on the controlling delivery effect of SiO2@LDH combined with anti‐cancer medicine from a new perspective. The fine properties synthetic SiO2@LDH‐VP16 (VP16: etoposide) are practiced to exhibit the nanoparticle's suppression on migration and invasion of non‐small cell lung cancer (NSCLC). Both in vitro and in vivo inspection shows that SiO2@LDH can help VP16 better function as an anti‐metastasis agent. On the other hand, anti‐angiogenic efficiency, co‐localization, as well as western blot are investigated to explain the possible mechanism. A clear mergence of SiO2@LDH‐VP16 and cytomembrane/microtubule may be observed from co‐location images. Results offer evidence that SiO2@LDH‐VP16 plays positions on cytomembrane and microtubules. It efficiently inhibits metastasis on NSCLC by reducing vascularization, and eliciting depression of the PI3K‐AKT and FAK‐Paxillin signaling pathways. SiO2@LDH‐VP16, the overall particle morphology, and function on anti‐metastasis and anti‐angiogenic may be tuned to give new opportunities for novel strategies for cancer therapy.

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“…The phosphor-protein array, using cell lysates of SKOV3-shCTHRC1 cells and SKOV3-NC cells as control, was performed by a Phospho-Antibody Array kit (CSP100, FullmoonBiosystems, CA) as previously described [27]. Briefly, cell lysates were biotin-labeled by biotin reagent in N, N-Dimethylformamide.…”

Section: Methodsmentioning

confidence: 99%

Collagen triple helix repeat containing 1 (CTHRC1) activates Integrin β3/FAK signaling and promotes metastasis in ovarian cancer

Guo

Yan

et al. 2017

J Ovarian Res

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BackgroundMetastasis is the major cause of morbidity and mortality in patients with epithelial ovarian cancer (EOC), however the mechanisms that underline this process are poorly understood. Collagen triple helix repeat containing-1 (CTHRC1) is a 28-kDa secreted protein reported to be involved in vascular remodeling, bone formation and morphogenesis. This study aimed to investigate the role of CTHRC1 in promoting the metastasis of EOC and to elucidate the underlying molecular mechanisms.MethodsThe biologic functions of CTHRC1 in metastasis were validated both in vivo and in vitro experiments. The phosphor-antibody microarray analysis and Co-immunoprecipitation were performed to detect and identify the integrin β3/FAK signaling pathway that mediated the function of CTHRC1. Seventy two EOC samples were analyzed for association between CTHRC1/integrin β3 expression and patient clinicopathological features.ResultsWe demonstrated that CTHRC1 enhances the biological behavior of EOC including cell migration, invasion, as well as its adhesion capability to cell-extracellular matrix in vitro. Additionally, CTHRC1 promoted metastatic spread of EOC cells in an i.p. ovarian xenograft model and this phenotype was primarily ascribed to the activation of integrin/FAK signaling. Mechanistically, we determined that FAK were phosphorylated on Tyr397, and were activated by integrin β3, which is important for the CTHRC1-mediated migratory and invasive ability of EOC cells in vitro and i.p. metastasis. In addition, we found that attenuated CTHRC1/integrin β3 expression predicted a poor prognostic phenotype and advanced clinical stage of EOC.ConclusionsOur results suggest that CTHRC1, a newly identified regulator of i.p. metastasis through activation of integrin β3/FAK signaling in EOC, may represent a potential therapeutic target for ovarian cancer.Electronic supplementary materialThe online version of this article (10.1186/s13048-017-0358-8) contains supplementary material, which is available to authorized users.

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A novel angiogenesis inhibitor impairs lovo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation

Cited by 35 publications

References 43 publications

ITGA2B and ITGA8 are predictive of prognosis in clear cell renal cell carcinoma patients

ITGA2B and ITGA8 are predictive of prognosis in clear cell renal cell carcinoma patients

Anti‐Metastatic and Anti‐Angiogenic Activities of Core–Shell SiO₂@LDH Loaded with Etoposide in Non‐Small Cell Lung Cancer

Collagen triple helix repeat containing 1 (CTHRC1) activates Integrin β3/FAK signaling and promotes metastasis in ovarian cancer

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A novel angiogenesis inhibitor impairs lovo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation

Cited by 35 publications

References 43 publications

ITGA2B and ITGA8 are predictive of prognosis in clear cell renal cell carcinoma patients

ITGA2B and ITGA8 are predictive of prognosis in clear cell renal cell carcinoma patients

Anti‐Metastatic and Anti‐Angiogenic Activities of Core–Shell SiO2@LDH Loaded with Etoposide in Non‐Small Cell Lung Cancer

Collagen triple helix repeat containing 1 (CTHRC1) activates Integrin β3/FAK signaling and promotes metastasis in ovarian cancer

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Anti‐Metastatic and Anti‐Angiogenic Activities of Core–Shell SiO₂@LDH Loaded with Etoposide in Non‐Small Cell Lung Cancer