title: Podocalyxin-like protein, linked to poor prognosis of pancreatic cancers, promotes cell invasion by binding to gelsolin.
abstract: The cell-adhesion glycoprotein PODXL is associated with an aggressive tumor phenotype in several forms of cancer. Here, we report that high PODXL expression was an independent predictor of worse overall survival of pancreatic cancer patients, and that PODXL promoted pancreatic cancer cell motility and invasion by physically binding to the cytoskeletal protein gelsolin. Suppression of PODXL or gelsolin decreased membrane protrusions with abundant peripheral actin structures, and in turn inhibited cell motility and invasion. Transfection of a PODXL-rescue construct renewed the expression of gelsolin bound to peripheral actin structures in cell protrusions, and abrogated the decreased cell protrusions caused by the knockdown of PODXL. Furthermore, transfection of a PODXL-rescue construct into pancreatic cancer cells in which both PODXL and gelsolin were suppressed failed to increase the formation of the protrusions. Thus, PODXL enhances motility and invasiveness through an increase in gelsolin-actin interactions in cell protrusions.
authors.affiliation: Department of Endoscopic Diagnostics and Therapeutics, Kochi Medical School, Kochi University, Nankoku, Japan. ktaniuchi@kochi-u.ac.jp.|Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Japan. ktaniuchi@kochi-u.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taniuchi
authors.affiliation: Department of Pathology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.affiliation: Department of Pathology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Naganuma
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Dabanaka
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hanazaki
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
mesh_terms: D000199:Actins / Q000378:metabolism; D014408:Biomarkers, Tumor; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D018260:Gelsolin / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D011485:Protein Binding; D021381:Protein Transport; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; D018260:Gelsolin; D012795:Sialoglycoproteins; C001643:podocalyxin
keywords: Actin-cytoskeleton; cell invasion; cell protrusions; pancreatic cancer; podocalyxin-like protein