RNAi-mediated ADAM9 gene silencing inhibits metastasis of adenoid cystic carcinoma cells

Xu, Qin; Liu, Xiuming; Cai, Yili; Yu, Youcheng; Chen, Wantao

doi:10.1007/s13277-010-0034-8

Cited by 19 publications

(16 citation statements)

References 24 publications

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“…These observations are in line with a previous study in which downregulation of ADAM9 in cystic carcinoma cells led to less lung metastasis, as determined by i.v. injection into nude mice (36). In agreement, overexpression of ADAM9 in lung cancer cells resulted in both brain and lung metastases, whereas mock-transfected cells only colonized the lungs (37,38).…”

Section: Discussionsupporting

confidence: 57%

Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9

Mammadova‐Bach¹,

Zigrino²,

Brucker³

et al. 2016

JCI Insight

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Section: Discussionsupporting

confidence: 57%

Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9

Mammadova‐Bach¹,

Zigrino²,

Brucker³

et al. 2016

JCI Insight

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“…These consecutive events result in alterations in a large number of genes and signaling pathways (35). ADAM9, a member of the ADAM family, appears to be involved in lung cancer progression and metastasis (19,20). A previous study demonstrated that the downregulation of endogenous ADAM9 by RNAi was capable of inhibiting adenoid cystic carcinoma cell growth and metastasis in vitro and in vivo (20).…”

Section: Discussionmentioning

confidence: 99%

“…ADAM9, a member of the ADAM family, appears to be involved in lung cancer progression and metastasis (19,20). A previous study demonstrated that the downregulation of endogenous ADAM9 by RNAi was capable of inhibiting adenoid cystic carcinoma cell growth and metastasis in vitro and in vivo (20). In addition, previous studies have confirmed that Stat3 is involved in cancer migration and invasion, and blocking the activity of Stat3 has been observed to inhibit cancer cell migration and invasion (6-16).…”

Section: Discussionmentioning

confidence: 99%

“…A previous study on lung cancer demonstrated that the overexpression of ADAM9 was able to enhance the adhesion and invasion abilities of NSCLC cells by modulating certain adhesion molecules and altering the sensitivity of NSCLC cells to growth factors, thereby promoting their metastatic capacity to the brain (19). It has been previously demonstrated that ADAM9 RNAi-based gene therapy is capable of inhibiting adenoid cystic carcinoma cell growth and metastasis in vitro and in vivo (20). In addition, a previous study by Chang et al (21) revealed that downregulating the expression of ADAM9 in A549 tumor cells via an RNA silencing approach significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis in vitro, in addition to suppressing tumor growth in vivo in an experimental mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Combined RNAi targeting human Stat3 and ADAM9 as gene therapy for non-small cell lung cancer

et al. 2015

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Abstract. Previous studies have demonstrated that human signal transducer and activator of transcription 3 (Stat3) and disintegrin and metalloproteinase 9 (ADAM9) are promising targets for RNA interference (RNAi)-based gene therapy for human non-small cell lung cancer (NSCLC). Thus, in the present study, the recombinant lentiviral (Lv) small hairpin (sh)RNA expression plasmids Lv/sh-Stat3 and Lv/sh-ADAM9, which targeted Stat3 and ADAM9, respectively, were constructed and subsequently infected into the A549 human NSCLC cell line. Cell proliferation, migration, invasion and apoptosis were determined in vitro in A549 cells following treatment with Lv/sh-Stat3 or Lv/sh-ADAM9 alone or in combination. In addition, the combined effect of Lv/sh-Stat3 and Lv/sh-ADAM9 gene therapy was evaluated in vivo using A549 xenograft models in nude mice. The in vitro experiments demonstrated that A549 cells treated with a combination of Lv/sh-Stat3 and Lv/sh-ADAM9 exhibited a significant additive effect in their cell proliferation, migration, invasion and apoptosis abilities, compared with A549 cells treated with Lv/sh-Stat3 or Lv/sh-ADAM9 alone. The in vivo experiments conducted in A549 xenograft tumor mouse models revealed that the combined treatment with Lv/sh-Stat3 and Lv/sh-ADAM9 exerted an additive effect on tumor growth inhibition, compared with the treatment with Lv/sh-Stat3 or Lv/sh-ADAM9 alone. These results suggested that combined RNAi gene therapy targeting human Stat3 and ADAM9 may be a novel and promising strategy for the treatment of NSCLC. IntroductionLung cancer is the most common cause of cancer-associated mortality globally, and non-small cell lung cancer (NSCLC) is responsible for ~85% of cases of lung cancer (1,2). Despite the wide utilization of chemotherapy and radiotherapy for the treatment of advanced NSCLC, patient outcomes remain poor, with only <15% of patients surviving >5 years following diagnosis (3). Metastasis is a major cause of morbidity and mortality in patients with NSCLC (4). Chemotherapy is the primary treatment for metastatic NSCLC (5). However, commonly used cytotoxic chemotherapeutic agents frequently display narrow therapeutic indices due to nonspecific cytotoxicity, undesirable side effects and intrinsic or acquired chemoresistance, which results in numerous cases of NSCLC being regarded as incurable (2). Therefore, the development of novel and effective therapeutic strategies for the treatment of NSCLC is required.Signal transducer and activator of transcription 3 (Stat3), a member of the STAT family, is capable of regulating the expression of target genes implicated in cell cycle progression, apoptosis, promotion of cellular transformation and aberrant cell proliferation (6). Therefore, Stat3 represents an attractive target for therapeutic intervention. Previous studies using RNA interference (RNAi), dominant negative Stat3 and small molecule inhibitors have demonstrated that the inhibition of Stat3 signaling suppresses tumor cell proliferation and invasion, induces apoptosis in vitro an...

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“…Oral medications to treat HCC are limited. Sorafenib, a multi-kinase inhibitor effective in enhancing overall survival of patients with advanced HCC [117], is the only oral drug recently approved by the US Food and Drug Administration. Sorafenib has antiproliferative activity in liver cancer cell lines.…”

Section: Mirnas In Treatment Stratification Of Hccmentioning

confidence: 99%

The role and clinical implications of microRNAs in hepatocellular carcinoma

Zhao

Yang

et al. 2012

Sci. China Life Sci.

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Hepatocellular carcinoma (HCC) is common and one of the most aggressive of all human cancers. Recent studies have indicated that miRNAs, a class of small noncoding RNAs that regulate gene expression post-transcriptionally, directly contribute to HCC by targeting many critical regulatory genes. Several miRNAs are involved in hepatitis B or hepatitis C virus replication and virus-induced changes, whereas others participate in multiple intracellular signaling pathways that modulate apoptosis, cell cycle checkpoints, and growth-factor-stimulated responses. When disturbed, these pathways appear to result in malignant transformation and ultimately HCC development. Recently, miRNAs circulating in the blood have acted as possible early diagnostic markers for HCC. These miRNA also could serve as indicators with respect to drug efficacy and be prognostic in HCC patients. Such biomarkers would assist stratification of HCC patients and help direct personalized therapy. Here, we summarize recent advances regarding the role of miRNAs in HCC development and progression. Our expectation is that these and ongoing studies will contribute to the understanding of the multiple roles of these small noncoding RNAs in liver tumorigenesis.

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RNAi-mediated ADAM9 gene silencing inhibits metastasis of adenoid cystic carcinoma cells

Cited by 19 publications

References 24 publications

Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9

Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9

Combined RNAi targeting human Stat3 and ADAM9 as gene therapy for non-small cell lung cancer

The role and clinical implications of microRNAs in hepatocellular carcinoma

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