title: Podocalyxin influences malignant potential by controlling epithelial-mesenchymal transition in lung adenocarcinoma.
abstract: 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.
authors.affiliation: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.|Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kusumoto
authors.affiliation: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shintani
authors.affiliation: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Kanzaki
authors.affiliation: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Funaki
authors.affiliation: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Minami
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Nagatomo
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Meinoshin
authors.initials: M
authors.lastname: Okumura
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015820:Cadherins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; D012795:Sialoglycoproteins; C001643:podocalyxin
keywords: Akt; epithelial mesenchymal transition; lung adenocarcinoma; phosphatidylinositol 3-kinase; podocalyxin