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Podocalyxin-like protein, linked to poor prognosis of pancreatic cancers, promotes cell invasion by binding to gelsolin.
- Source :
-
Cancer science [Cancer Sci] 2016 Oct; Vol. 107 (10), pp. 1430-1442. Date of Electronic Publication: 2016 Sep 02. - Publication Year :
- 2016
-
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.<br /> (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Actins metabolism
Biomarkers, Tumor
Carcinoma, Pancreatic Ductal genetics
Carcinoma, Pancreatic Ductal metabolism
Carcinoma, Pancreatic Ductal mortality
Carcinoma, Pancreatic Ductal pathology
Cell Line, Tumor
Cell Movement genetics
Female
Gene Expression
Gene Knockdown Techniques
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Neoplasm Metastasis
Neoplasm Staging
Pancreatic Neoplasms metabolism
Pancreatic Neoplasms pathology
Prognosis
Protein Binding
Protein Transport
Gelsolin metabolism
Pancreatic Neoplasms genetics
Pancreatic Neoplasms mortality
Sialoglycoproteins genetics
Sialoglycoproteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 107
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 27461278
- Full Text :
- https://doi.org/10.1111/cas.13018