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  • 1
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2008
    In:  Clinical & Experimental Metastasis Vol. 25, No. 5 ( 2008-9), p. 537-548
    In: Clinical & Experimental Metastasis, Springer Science and Business Media LLC, Vol. 25, No. 5 ( 2008-9), p. 537-548
    Type of Medium: Online Resource
    ISSN: 0262-0898 , 1573-7276
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2008
    detail.hit.zdb_id: 1496876-9
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2021-6-7)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-6-7)
    Abstract: Focusing on antiangiogenesis may provide promising choices for treatment of gastric cancer (GC). This study aimed to investigate the mechanistic role of BCAT1 in the pathogenesis of GC, particularly in angiogenesis. Methods Bioinformatics and clinical samples analysis were used to investigate the expression and potential mechanism of BCAT1 in GC. BGC823 cells with BCAT1 overexpression or silencing were induced by lentiviral transduction. Cell phenotypes and angiogenesis were evaluated. The relevant proteins were quantized by Western blotting, immunohistochemistry, or immunofluorescence. Xenograft models were constructed to confirm the role of BCAT1 in vivo . Results BCAT1 was overexpressed in GC patients and associated with lower survival. BCAT1 expression was correlated with proliferation-, invasion-, or angiogenesis-related markers expression and pathways. Silencing BCAT1 expression suppressed cell viability, colony formation, cycle progression, invasion, and angiogenesis of BGC823 cells, as well as the tumor growth of xenograft models, whereas overexpressing BCAT1 had the opposite results both in vitro and in vivo . Bioinformatics analysis and Western blotting demonstrated that BCAT1 activated the PI3K/AKT/mTOR pathway. The addition of LY294002 reversed the tumor growth induced by BCAT1 overexpression, further verifying this mechanism. Conclusion BCAT1 might act as an oncogene by facilitating proliferation, invasion, and angiogenesis through activation of the PI3K/AKT/mTOR pathway. This finding could aid the optimization of antiangiogenesis strategies.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
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  • 3
    In: Carcinogenesis, Oxford University Press (OUP), Vol. 30, No. 10 ( 2009-10), p. 1660-1669
    Type of Medium: Online Resource
    ISSN: 1460-2180 , 0143-3334
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2009
    detail.hit.zdb_id: 1474206-8
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  • 4
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2011
    In:  Clinical Oncology and Cancer Research Vol. 8, No. 3 ( 2011-9), p. 138-143
    In: Clinical Oncology and Cancer Research, Springer Science and Business Media LLC, Vol. 8, No. 3 ( 2011-9), p. 138-143
    Type of Medium: Online Resource
    ISSN: 1674-5361 , 1868-324X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2011
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2020
    In:  Cell Death & Disease Vol. 11, No. 10 ( 2020-10-16)
    In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 11, No. 10 ( 2020-10-16)
    Abstract: Recent studies have demonstrated that gastric cancer stem cells (CSCs) are a rare sub-group of gastric cancer (GC) cells and have an important role in promoting the tumor growth and progression of GC. In the present study, we demonstrated that the glycolytic enzyme Enolase 1 (ENO1) was involved in the regulation of the stem cell-like characteristics of GC cells, as compared to the parental cell lines PAMC-82 and SNU16, the expression of ENO1 in spheroids markedly increased. We then observed that ENO1 could enhance stem cell-like characteristics, including self-renewal capacity, cell invasion and migration, chemoresistance, and even the tumorigenicity of GC cells. ENO1 is known as an enzyme that is involved in glycolysis, but our results showed that ENO1 could markedly promote the glycolytic activity of cells. Furthermore, inhibiting glycolysis activity using 2-deoxy- d -glucose treatment significantly reduced the stemness of GC cells. Therefore, ENO1 could improve the stemness of CSCs by enhancing the cells’ glycolysis. Subsequently, to further confirm our results, we found that the inhibition of ENO1 using AP-III-a4 (ENOblock) could reduce the stemness of GC cells to a similar extent as the knockdown of ENO1 by shRNA. Finally, increased expression of ENO1 was related to poor prognosis in GC patients. Taken together, our results demonstrated that ENO1 is a significant biomarker associated with the stemness of GC cells.
    Type of Medium: Online Resource
    ISSN: 2041-4889
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2541626-1
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2023
    In:  Stem Cell Research & Therapy Vol. 14, No. 1 ( 2023-09-27)
    In: Stem Cell Research & Therapy, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-09-27)
    Abstract: Identification of promising targeted antigens that exhibited cancer-specific expression is a crucial step in the development of novel antibody-targeted therapies. We here aimed to investigate the anti-tumor activity of a novel monoclonal antibody (mAb) 11C9 and identify the antibody tractable target in the hepatocellular cancer stem cells (HCSCs). Methods The identification of the targeted antigen was conducted using SDS-PAGE, western blot, mass spectrometry, and co-immunoprecipitation. Silence of HSP90 was induced by siRNA interference. Positive cells were sorted by fluorescence-activated cell sorting. Double-immunofluorescent (IF) staining and two-color flow cytometry detected the co-expression. Self-renewal, invasion, and drug resistance were assessed by sphere formation, matrigel-coated Transwell assay, and CCK-8 assay, respectively. Tumorigenicity was evaluated in mouse xenograft models. RNA-seq and bioinformatics analysis were performed to explore the mechanism of mAb 11C9 and potential targets. Results MAb 11C9 inhibited invasion and self-renewal abilities of HCC cell lines and reversed the cisplatin resistance. HSP90 (~ 95 kDa) was identified as a targeted antigen of mAb 11C9. Tissue microarrays and online databases revealed that HSP90 was overexpressed in HCC and associated with a poor prognosis. FACS and double-IF staining showed the co-expression of HSP90 and CSCs markers (CD90 and ESA). In vitro and in vivo demonstrated the tumorigenic potentials of HSP90. The inhibition of HSP90 by siRNA interference or 17-AAG inhibitor both decreased the number of invasion, sphere cells, and CD90 + or ESA + cells, as well as reversed the resistance. Bioinformatics analysis and western blot verified that HSP90 activated Wnt/β-catenin signaling. Conclusions The study preliminarily revealed the anti-tumor activity of mAb 11C9. More importantly, we identified HSP90 as a targeted antigen of mAb 11C9, which functions as an oncogene in phenotype shaping, stemness maintenance, and therapeutic resistance by activating Wnt/β-catenin signaling.
    Type of Medium: Online Resource
    ISSN: 1757-6512
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2548671-8
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  • 7
    In: Cancer Medicine, Wiley, Vol. 12, No. 4 ( 2023-02), p. 4510-4520
    Abstract: Cancer stem cells (CSCs) are responsible for drug resistance, cancer relapse, and metastasis. Here, we report the first analysis of Palladin expression and its impacts on stem cell‐like properties in lung cancer. Methods Tissue microarrays were used to investigate Palladin expression and its association with prognosis. Immunofluorescence (IF), flow fluorescence assay, and Western blot were performed to detect Palladin expression in 6 NSCLC cell lines. Cell phenotypes and drug resistance were evaluated. Xenograft models were constructed to confirm the role of Palladin in vivo. Results By using the tissue microarrays, Palladin was identified to be highly expressed in the cytoplasm, specifically in the cytomembrane of NSCLC, and its high expression is associated with poor prognosis. Palladin is widely expressed and enriched in the sphere cells. The in vitro and in vivo studies showed that Palladin promoted stem cell‐like properties, including cell viability, invasion, migration, self‐renewal abilities, taxol resistance, and tumorigenicity. Western blot revealed that Palladin promoted the accumulation of β‐catenin and activated Wnt/β‐catenin signaling. Tissue microarrays analysis further confirmed the positive correlation between Palladin and β‐catenin. Wnt/β‐catenin pathway inhibitor blocked the Palladin‐induced enhancement of sphere‐forming. Conclusions Palladin might act as an oncogene by promoting CSCs‐like properties and tumorigenicity of NSCLC cells via the Wnt/β‐catenin signaling pathway. Besides, Palladin was identified to have the potential as a cell surface marker for LCSCs identification. These findings provide a possible target for developing putative agents targeted to LCSCs.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2659751-2
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Cell Death Discovery Vol. 7, No. 1 ( 2021-10-11)
    In: Cell Death Discovery, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2021-10-11)
    Abstract: The fatality rate of non-small cell lung cancer (NSCLC) has been high due to the existence of cancer stem cells (CSCs). Non-muscle myosin heavy chain 9 (MYH9) can promote the progression of various tumors, but its effect on the stem cell-like characteristics of lung cancer cells (LCCs) has not been clarified. Our research found that the stemness characteristics of LCCs were significantly enhanced by the overexpression of MYH9, and the knockout of MYH9 had the opposite effects. The in vivo with inhibitor blebbistatin further confirmed the effect of MYH9 on the stem cell-like behavior of LCCs. Furthermore, western blotting showed that the expression level of CSCs markers (CD44, SOX2, Nanog, CD133, and OCT4) was also regulated by MYH9. Mechanistic studies have shown that MYH9 regulates stem cell-like features of LCCs by regulating the mTOR signaling pathway, which was supported by sphere formation experiments after LCCs were treated with inhibitors Rapamycin and CHIR-99021. Importantly, high expression of MYH9 in lung cancer is positively correlated with poor clinical prognosis and is an independent risk factor for patients with NSCLC.
    Type of Medium: Online Resource
    ISSN: 2058-7716
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2842546-7
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  • 9
    In: Precision Radiation Oncology, Wiley, Vol. 3, No. 2 ( 2019-06), p. 44-51
    Abstract: The incidence and mortality rate of lung cancer ranks first among all malignant tumors. Lymph node metastasis is the most common mode of metastasis in lung cancer, and it is also an important indicator for treatment strategies and prognosis. Several studies have shown that the carboxypeptidase family plays important roles in cancer metastasis. In the present study, we investigated the effect of carboxypeptidase A4 ( CPA4 ) on human lung cancer cells, and the clinical significance of its levels in lung cancer tissues and corresponding lymph node metastasis tissues. Methods Real‐time quantitative polymerase chain reaction and western blotting were used to detect the expression levels of CPA4 in cancer cells after transfecting them with CPA4 interference sequence (siRNA‐CPA4) and the negative control sequence. Transwell assay with/without Matrigel was used to assess the effect of CPA4 on cell invasion and migration. CPA4 expression was detected in eight normal lung tissues, 46 lung cancer tissues, and the corresponding lymph node metastasis tissues using immunohistochemistry. Results Reverse transcription polymerase chain reaction and western blot showed that siRNA‐CPA4 significantly decreased CPA4 mRNA levels in H226 and SKMES‐1 cells compared with the control cells. Knockdown of CPA4 in lung cancer cells significantly inhibited cell invasion by 62.3% and 77.3% in H226 and SKMES‐1 cell, respectively. Furthermore, siRNA‐CPA4 significantly suppressed cell migration in H226 and SKMES‐1 cells by 48.1% and 42.4%, respectively. Immunohistochemistry results showed that the positive expression rate of CPA4 in lung normal tissues, cancer tissues, and lymph node metastatic tissues was 12.5% (1/8), 50.0% (23/46), and 76.1% (35/46), respectively. Importantly, the levels of CPA4 in the lymph node metastatic tissues were significantly higher than those in corresponding primary lung cancer tissues ( t  = 5.176, P   〈  0.001). The clinical correlation analysis showed that high levels of CPA4 were closely associated with the tumor pathology type, differentiation, and stage; however, there was no significant correlation with the age, sex, and depth of invasion. Conclusions CPA4 promoted the invasion and migration of human lung cancer cells, H226, and SKMES‐1, in vitro . The levels of CPA4 were gradually elevated in primary lung cancer and corresponding lymph node metastasis tissues, and CPA4 could be a potential candidate therapeutic target for lung cancer.
    Type of Medium: Online Resource
    ISSN: 2398-7324 , 2398-7324
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2899107-2
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  • 10
    In: Investigational New Drugs, Springer Science and Business Media LLC, Vol. 39, No. 4 ( 2021-08), p. 949-960
    Type of Medium: Online Resource
    ISSN: 0167-6997 , 1573-0646
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2009846-7
    SSG: 15,3
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