Cargando…
Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma
Epithelial–mesenchymal transition (EMT) plays an important role in the progression of lung carcinoma. Podocalyxin (PODXL), which belongs to the CD34 family and regulates cell morphology, has been linked to EMT in lung cancer, and PODXL overexpression is associated with poor prognosis in several diff...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378270/ https://www.ncbi.nlm.nih.gov/pubmed/28004467 http://dx.doi.org/10.1111/cas.13142 |
_version_ | 1782519415212867584 |
---|---|
author | Kusumoto, Hidenori Shintani, Yasushi Kanzaki, Ryu Kawamura, Tomohiro Funaki, Soichiro Minami, Masato Nagatomo, Izumi Morii, Eiichi Okumura, Meinoshin |
author_facet | Kusumoto, Hidenori Shintani, Yasushi Kanzaki, Ryu Kawamura, Tomohiro Funaki, Soichiro Minami, Masato Nagatomo, Izumi Morii, Eiichi Okumura, Meinoshin |
author_sort | Kusumoto, Hidenori |
collection | PubMed |
description | Epithelial–mesenchymal transition (EMT) plays an important role in the progression of lung carcinoma. Podocalyxin (PODXL), which belongs to the CD34 family and regulates cell morphology, has been linked to EMT in lung cancer, and PODXL overexpression is associated with poor prognosis in several different classes of cancers. The aim of this study was to clarify the role of PODXL overexpression in EMT in lung cancer, and to determine the prognostic value of PODXL overexpression in tumors from lung cancer patients. The morphology, EMT marker expression, and migration and invasion abilities of engineered A549 PODXL‐knockdown (KD) or PODXL‐overexpression (OE) lung adenocarcinoma cells were examined. PODXL expression levels were assessed by immunohistochemistry in 114 human clinical lung adenocarcinoma specimens and correlated with clinical outcomes. PODXL‐KD cells were epithelial in shape, whereas PODXL‐OE cells displayed mesenchymal morphology. Epithelial markers were upregulated in PODXL‐KD cells and downregulated in PODXL‐OE 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 EMT of PODXL‐OE cells, while a transforming growth factor inhibitor did not, suggesting that PODXL induces EMT of lung adenocarcinoma cells via the phosphatidylinositol 3‐kinase pathway. In lung adenocarcinoma clinical specimens, PODXL 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 PODXL. PODXL overexpression induces EMT in lung adenocarcinoma and contributes to tumor progression. |
format | Online Article Text |
id | pubmed-5378270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53782702017-04-07 Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma Kusumoto, Hidenori Shintani, Yasushi Kanzaki, Ryu Kawamura, Tomohiro Funaki, Soichiro Minami, Masato Nagatomo, Izumi Morii, Eiichi Okumura, Meinoshin Cancer Sci Original Articles Epithelial–mesenchymal transition (EMT) plays an important role in the progression of lung carcinoma. Podocalyxin (PODXL), which belongs to the CD34 family and regulates cell morphology, has been linked to EMT in lung cancer, and PODXL overexpression is associated with poor prognosis in several different classes of cancers. The aim of this study was to clarify the role of PODXL overexpression in EMT in lung cancer, and to determine the prognostic value of PODXL overexpression in tumors from lung cancer patients. The morphology, EMT marker expression, and migration and invasion abilities of engineered A549 PODXL‐knockdown (KD) or PODXL‐overexpression (OE) lung adenocarcinoma cells were examined. PODXL expression levels were assessed by immunohistochemistry in 114 human clinical lung adenocarcinoma specimens and correlated with clinical outcomes. PODXL‐KD cells were epithelial in shape, whereas PODXL‐OE cells displayed mesenchymal morphology. Epithelial markers were upregulated in PODXL‐KD cells and downregulated in PODXL‐OE 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 EMT of PODXL‐OE cells, while a transforming growth factor inhibitor did not, suggesting that PODXL induces EMT of lung adenocarcinoma cells via the phosphatidylinositol 3‐kinase pathway. In lung adenocarcinoma clinical specimens, PODXL 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 PODXL. PODXL overexpression induces EMT in lung adenocarcinoma and contributes to tumor progression. John Wiley and Sons Inc. 2017-04-03 2017-03 /pmc/articles/PMC5378270/ /pubmed/28004467 http://dx.doi.org/10.1111/cas.13142 Text en © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Kusumoto, Hidenori Shintani, Yasushi Kanzaki, Ryu Kawamura, Tomohiro Funaki, Soichiro Minami, Masato Nagatomo, Izumi Morii, Eiichi Okumura, Meinoshin Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma |
title | Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma |
title_full | Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma |
title_fullStr | Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma |
title_full_unstemmed | Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma |
title_short | Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma |
title_sort | podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378270/ https://www.ncbi.nlm.nih.gov/pubmed/28004467 http://dx.doi.org/10.1111/cas.13142 |
work_keys_str_mv | AT kusumotohidenori podocalyxininfluencesmalignantpotentialbycontrollingepithelialmesenchymaltransitioninlungadenocarcinoma AT shintaniyasushi podocalyxininfluencesmalignantpotentialbycontrollingepithelialmesenchymaltransitioninlungadenocarcinoma AT kanzakiryu podocalyxininfluencesmalignantpotentialbycontrollingepithelialmesenchymaltransitioninlungadenocarcinoma AT kawamuratomohiro podocalyxininfluencesmalignantpotentialbycontrollingepithelialmesenchymaltransitioninlungadenocarcinoma AT funakisoichiro podocalyxininfluencesmalignantpotentialbycontrollingepithelialmesenchymaltransitioninlungadenocarcinoma AT minamimasato podocalyxininfluencesmalignantpotentialbycontrollingepithelialmesenchymaltransitioninlungadenocarcinoma AT nagatomoizumi podocalyxininfluencesmalignantpotentialbycontrollingepithelialmesenchymaltransitioninlungadenocarcinoma AT moriieiichi podocalyxininfluencesmalignantpotentialbycontrollingepithelialmesenchymaltransitioninlungadenocarcinoma AT okumurameinoshin podocalyxininfluencesmalignantpotentialbycontrollingepithelialmesenchymaltransitioninlungadenocarcinoma |