Abstract:
:The establishment of a proangiogenic phenotype and epithelial-to-mesenchymal transition (EMT) are considered as critical events that promote the induction of invasive growth in epithelial tumors, and stimulation of lymphangiogenesis is believed to confer the capacity for early dissemination to cancer cells. Recent research has revealed substantial interdependence between these processes at the molecular level as they rely on common signaling networks. Of great interest are the molecular mechanisms of (lymph-)angiogenesis and EMT associated with the earliest stages of transition from intraepithelial development to invasive growth, as they could provide the source of potentially valuable tools for targeting tumor metastasis. However, in the case of early-stage cervical cancer, the players of (lymph-)angiogenesis and EMT processes still remain substantially uncharacterized. In this study, we used RNA sequencing to compare transcriptomes of HPV(+) preinvasive neoplastic lesions and early-stage invasive carcinoma of the cervix and to identify (lymph-)angiogenesis- and EMT-related genes and pathways that may underlie early acquisition of invasive phenotype and metastatic properties by cervical cancer cells. Second, we applied flow cytometric analysis to evaluate the expression of three key lymphangiogenesis/EMT markers (VEGFR3, MET, and SLUG) in epithelial cells derived from enzymatically treated tissue specimens. Overall, among 201 differentially expressed genes, a considerable number of (lymph-)angiogenesis and EMT regulatory factors were identified, including genes encoding cytokines, growth factor receptors, transcription factors, and adhesion molecules. Pathway analysis confirmed enrichment for angiogenesis, epithelial differentiation, and cell guidance pathways at transition from intraepithelial neoplasia to invasive carcinoma and suggested immune-regulatory/inflammatory pathways to be implicated in initiation of invasive growth of cervical cancer. Flow cytometry showed cell phenotype-specific expression pattern for VEGFR3, MET, and SLUG and revealed correlation with the amount of tumor-infiltrating lymphocytes at the early stages of cervical cancer progression. Taken together, these results extend our understanding of driving forces of angiogenesis and metastasis in HPV-associated cervical cancer and may be useful for developing new treatments.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Kurmyshkina O,Kovchur P,Schegoleva L,Volkova Tdoi
10.3390/ijms21186515subject
Has Abstractpub_date
2020-09-06 00:00:00issue
18issn
1422-0067pii
ijms21186515journal_volume
21pub_type
杂志文章abstract::Glutathione synthetases catalyze the ATP-dependent synthesis of glutathione from l-γ-glutamyl- l-cysteine and glycine. Although these enzymes have been sequenced and characterized from a variety of biological sources, their exact catalytic mechanism is not fully understood and nothing is known about their adaptation a...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms12096312
更新日期:2011-01-01 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2020-09-02 00:00:00
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journal_title:International journal of molecular sciences
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doi:10.3390/ijms161024243
更新日期:2015-10-14 00:00:00
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journal_title:International journal of molecular sciences
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更新日期:2015-12-04 00:00:00
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journal_title:International journal of molecular sciences
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更新日期:2018-09-03 00:00:00
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journal_title:International journal of molecular sciences
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doi:10.3390/ijms20081921
更新日期:2019-04-18 00:00:00
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journal_title:International journal of molecular sciences
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更新日期:2020-01-27 00:00:00
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journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19102994
更新日期:2018-09-30 00:00:00
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journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms17091531
更新日期:2016-09-12 00:00:00
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journal_title:International journal of molecular sciences
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doi:10.3390/ijms151221913
更新日期:2014-11-28 00:00:00
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journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms14022601
更新日期:2013-01-28 00:00:00
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doi:10.3390/ijms18081743
更新日期:2017-08-11 00:00:00
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journal_title:International journal of molecular sciences
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更新日期:2019-11-27 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2012-12-07 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2008-06-01 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2019-08-08 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2012-12-24 00:00:00
abstract::n/a. ...
journal_title:International journal of molecular sciences
pub_type: 评论,杂志文章
doi:10.3390/ijms18050994
更新日期:2017-05-05 00:00:00