Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma
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- Hidenori Kusumoto
- Department of General Thoracic Surgery Osaka University Graduate School of Medicine Osaka Japan
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- Yasushi Shintani
- Department of General Thoracic Surgery Osaka University Graduate School of Medicine Osaka Japan
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- Ryu Kanzaki
- Department of General Thoracic Surgery Osaka University Graduate School of Medicine Osaka Japan
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- Tomohiro Kawamura
- Department of General Thoracic Surgery Osaka University Graduate School of Medicine Osaka Japan
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- Soichiro Funaki
- Department of General Thoracic Surgery Osaka University Graduate School of Medicine Osaka Japan
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- Masato Minami
- Department of General Thoracic Surgery Osaka University Graduate School of Medicine Osaka Japan
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- Izumi Nagatomo
- Department of Respiratory Medicine, Allergy and Rheumatic Disease Osaka University Graduate School of Medicine Osaka Japan
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- Eiichi Morii
- Department of Pathology Osaka University Graduate School of Medicine Osaka Japan
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- Meinoshin Okumura
- Department of General Thoracic Surgery Osaka University Graduate School of Medicine Osaka Japan
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説明
<jats:p>Epithelial–mesenchymal transition (<jats:styled-content style="fixed-case">EMT</jats:styled-content>) plays an important role in the progression of lung carcinoma. Podocalyxin (<jats:styled-content style="fixed-case">PODXL</jats:styled-content>), which belongs to the <jats:styled-content style="fixed-case">CD</jats:styled-content>34 family and regulates cell morphology, has been linked to <jats:styled-content style="fixed-case">EMT</jats:styled-content> in lung cancer, and <jats:styled-content style="fixed-case">PODXL</jats:styled-content> overexpression is associated with poor prognosis in several different classes of cancers. The aim of this study was to clarify the role of <jats:styled-content style="fixed-case">PODXL</jats:styled-content> overexpression in <jats:styled-content style="fixed-case">EMT</jats:styled-content> in lung cancer, and to determine the prognostic value of <jats:styled-content style="fixed-case">PODXL</jats:styled-content> overexpression in tumors from lung cancer patients. The morphology, <jats:styled-content style="fixed-case">EMT</jats:styled-content> marker expression, and migration and invasion abilities of engineered A549 <jats:styled-content style="fixed-case">PODXL</jats:styled-content>‐knockdown (<jats:styled-content style="fixed-case">KD</jats:styled-content>) or <jats:styled-content style="fixed-case">PODXL</jats:styled-content>‐overexpression (<jats:styled-content style="fixed-case">OE</jats:styled-content>) lung adenocarcinoma cells were examined. <jats:styled-content style="fixed-case">PODXL</jats:styled-content> expression levels were assessed by immunohistochemistry in 114 human clinical lung adenocarcinoma specimens and correlated with clinical outcomes. <jats:styled-content style="fixed-case">PODXL</jats:styled-content>‐<jats:styled-content style="fixed-case">KD</jats:styled-content> cells were epithelial in shape, whereas <jats:styled-content style="fixed-case">PODXL</jats:styled-content>‐<jats:styled-content style="fixed-case">OE</jats:styled-content> cells displayed mesenchymal morphology. Epithelial markers were upregulated in <jats:styled-content style="fixed-case">PODXL</jats:styled-content>‐<jats:styled-content style="fixed-case">KD</jats:styled-content> cells and downregulated in <jats:styled-content style="fixed-case">PODXL</jats:styled-content>‐<jats:styled-content style="fixed-case">OE</jats:styled-content> cells, whereas mesenchymal markers were downregulated in the former and upregulated in the latter. A highly selective inhibitor of phosphatidylinositol 3‐kinase‐Akt signaling attenuated <jats:styled-content style="fixed-case">EMT</jats:styled-content> of <jats:styled-content style="fixed-case">PODXL</jats:styled-content>‐<jats:styled-content style="fixed-case">OE</jats:styled-content> cells, while a transforming growth factor inhibitor did not, suggesting that <jats:styled-content style="fixed-case">PODXL</jats:styled-content> induces <jats:styled-content style="fixed-case">EMT</jats:styled-content> of lung adenocarcinoma cells via the phosphatidylinositol 3‐kinase pathway. In lung adenocarcinoma clinical specimens, <jats:styled-content style="fixed-case">PODXL</jats:styled-content> expression was detected in minimally invasive and invasive adenocarcinoma, but not in non‐invasive adenocarcinoma. Disease free survival and cancer‐specific survival were significantly worse for patients whose tumors overexpressed <jats:styled-content style="fixed-case">PODXL</jats:styled-content>. <jats:styled-content style="fixed-case">PODXL</jats:styled-content> overexpression induces <jats:styled-content style="fixed-case">EMT</jats:styled-content> in lung adenocarcinoma and contributes to tumor progression.</jats:p>
収録刊行物
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- Cancer Science
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Cancer Science 108 (3), 528-535, 2017-03
Wiley
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キーワード
- Epithelial-Mesenchymal Transition
- Lung Neoplasms
- Sialoglycoproteins
- Adenocarcinoma of Lung
- Original Articles
- Adenocarcinoma
- Cadherins
- Disease-Free Survival
- A549 Cells
- Cell Movement
- Cell Line, Tumor
- Disease Progression
- Humans
- Neoplasm Invasiveness
- RNA Interference
- RNA, Small Interfering
- Phosphoinositide-3 Kinase Inhibitors
詳細情報 詳細情報について
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- CRID
- 1360846643076339200
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- ISSN
- 13497006
- 13479032
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- PubMed
- 28004467
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE