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  • American Association for Cancer Research (AACR)  (2)
  • Xie, Xiaoming  (2)
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  • American Association for Cancer Research (AACR)  (2)
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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1912-1912
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1912-1912
    Abstract: Purpose: Pharmacology-based target identification has become a novel stratey leading to the discovery of novel pathological biomarkers. Ellagic acid (EA), a dietary polyphenol compound, exhibits potent anticancer activities, whereas the underlying mechanisms remain unclear. This study sought to determine the role and regulation of ACTN4 expression in human breast cancer metastasis and EA-based therapy. Experimental Design: The anti-metastasis ability of EA was validated by MMTV-PyMT mice and in vitro cell models. Drug affiity responsive target stability (DARTS) was utilized to identify ACTN4 as the direct target of EA in breast breast cancer stem cells (CSCs). The metastatic regulated mechanisms of ACTN4 were assessed by CSC-related assays including mammosphere formation, tumorigenic ability, reattachment differentiation and signaling pathway analysis. The clinical significance of ACTN4 was based on human tissue microarray analysis and TCGA database exploration. Results: EA inhibited breast cancer growth and metastasis via directly targeting ACTN4 in vitro and in vivo, accompanied with limited CSCs population. ACTN4 knockdown resulted in blockage of malignant cell proliferation, colony formation and ameliorated metastasis potency. ACTN4 positive CSCs exhibited higher ESA+ proportion, increased mammosphere-formation ability, as well as enhanced in vivo tumorigenesis ability. Increased ACTN4 expression was directly associated with later cancer stage, increased incidence of metastasis, and poor overall survival period. Conclusions: ACTN4 plays an important role in breast CSCs-related metastasis and is a novel therapeutic target of EA treatment. Note: This abstract was not presented at the meeting. Citation Format: Neng Wang, Zhiyu Wang, Xiaoming Xie. Actn4, a novel therapeutic target of dietary ellagic acid, promotes breast cancer metastasis via mediating cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1912. doi:10.1158/1538-7445.AM2017-1912
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 21, No. 7 ( 2012-07-01), p. 1176-1184
    Abstract: Background: The TGF-β signaling pathway plays a significant role in the carcinogenic process of breast cancer. Methods: We systematically evaluated associations of common variants in TGF-β signaling pathway genes with breast cancer risk using a multistage, case–control study among Asian women. Results: In the first stage, 341 single-nucleotide polymorphisms with minor allele frequencies ≥ 0.05 across 11 genes were evaluated among 2,926 cases and 2,380 controls recruited as a part of the Shanghai Breast Cancer Genetics Study (SBCGS). In the second stage, 20 SNPs with promising associations were evaluated among an additional 1,890 cases and 2,000 controls from the SBCGS. One variant, TGFBR2 rs1078985, had highly consistent and significant associations with breast cancer risk among participants in both study stages, as well as promising results from in silico analysis. Additional genotyping was carried out among 2,475 cases and 2,343 controls from the SBCGS, as well as among 5,077 cases and 5,384 controls from six studies in the Asian Breast Cancer Consortium (stage III). Pooled analysis of all data indicated that minor allele homozygotes (GG) of TGFBR2 rs1078985 had a 24% reduced risk of breast cancer compared with major allele carriers (AG or AA; OR, 0.76; 95% CI, 0.65–0.89; P = 8.42 × 10−4). Conclusion: These findings support a role for common genetic variation in TGF-β signaling pathway genes, specifically in TGFBR2, in breast cancer susceptibility. Impact: These findings may provide new insights into the etiology of breast cancer as well as future potential therapeutic targets. Cancer Epidemiol Biomarkers Prev; 21(7); 1176–84. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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