Article thumbnail

Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition

By Xiaobo Meng, Peyman Ezzati and John A. Wilkins

Abstract

Epithelial mesenchymal transition (EMT) is characterized by the development of mesenchymal properties such as a fibroblast-like morphology with altered cytoskeletal organization and enhanced migratory potential. We report that the expression of podocalyxin (PODXL), a member of the CD34 family, is markedly increased during TGF-β induced EMT. PODXL is enriched on the leading edges of migrating A549 cells. Silencing of podocalyxin expression reduced cell ruffle formation, spreading, migration and affected the expression patterns of several proteins that normally change during EMT (e.g., vimentin, E-cadherin). Cytoskeletion assembly in EMT was also found to be dependent on the production of podocalyin. Compositional analysis of podocalyxin containing immunoprecipitates revealed that collagen type 1 was consistently associated with these isolates. Collagen type 1 was also found to co-localize with podocalyxin on the leading edges of migrating cells. The interactions with collagen may be a critical aspect of podocalyxin function. Podocalyxin is an important regulator of the EMT like process as it regulates the loss of epithelial features and the acquisition of a motile phenotype

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3075272
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2001). A new role for E12/E47 in the repression of E-cadherin expression and epithelialmesenchymal transitions.
  2. (2009). A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition.
  3. (1985). An epithelial scatter factor released by embryo fibroblasts.
  4. (2001). Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin.
  5. (2007). Cano A
  6. (2000). Cell surface-bound collagenase-1 and focal substrate degradation stimulate the rear release of motile vascular smooth muscle cells.
  7. (1978). Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides.
  8. (2006). Complex networks orchestrate epithelialmesenchymal transitions.
  9. (2009). Cortactin interacts with podocalyxin and mediates morphological change of podocytes through its phosphorylation.
  10. (2005). DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells.
  11. (2006). Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype.
  12. (2003). Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis.
  13. (2007). Endothelial-to-mesenchymal transition contributes to cardiac fibrosis.
  14. (2008). Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis.
  15. (2009). Epithelial-mesenchymal transitions in development and disease.
  16. (2010). Epithelialmesenchymal transition in cancer development and its clinical significance.
  17. (2002). Evidence that fibroblasts derive from epithelium during tissue fibrosis.
  18. (2008). Expression of podocalyxin enhances the adherence, migration, and intercellular communication of cells.
  19. (2000). Expression of podocalyxin inhibits cell-cell adhesion and modifies junctional properties in Madin-Darby canine kidney cells.
  20. (2004). Fibroblast growth factor-2 and remodeled type I collagen control membrane protrusion in human vascular smooth muscle cells: biphasic activation of Rac1.
  21. (2010). Hertig A [Interstitial fibrosis in renal grafts: On the way to a better detection.]. Nephrol Ther Available at: http:// www.ncbi.nlm.nih.gov/pubmed/20627838.
  22. (1984). Identification and characterization of podocalyxin—the major sialoprotein of the renal glomerular epithelial cell.
  23. (2008). Molecular and pathological signatures of epithelial-mesenchymal transitions at the cancer invasion front.
  24. (2008). Novel functions of the CD34 family.
  25. (2002). PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2.
  26. (2010). Phosphoproteomic study of human tubular epithelial cell in response to transforming growth factorbeta-1-induced epithelial-to-mesenchymal transition.
  27. (2007). Podocalyxin enhances the adherence of cells to platelets.
  28. (2007). Podocalyxin increases the aggressive phenotype of breast and prostate cancer cells in vitro through its interaction with ezrin.
  29. (2002). Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways.
  30. (2006). Relevance of the stroma and epithelial-mesenchymal transition (EMT) for the rheumatic diseases.
  31. (2009). Secretome-based proteomic profiling of Ras-transformed MDCK cells reveals extracellular modulators of epithelial-mesenchymal transition.
  32. (2005). SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions.
  33. (2008). Snail promotes Wnt target gene expression and interacts with beta-catenin.
  34. (2009). Subcellular fractionation of TGF-beta1-stimulated lung epithelial cells: a novel proteomic approach for identifying signaling intermediates.
  35. (2009). Temporal quantitative proteomics by iTRAQ 2D-LC-MS/MS and corresponding mRNA expression analysis identify post-transcriptional modulation of actincytoskeleton regulators during TGF-beta-Induced epithelial-mesenchymal transition.
  36. (2009). TGF-beta-induced epithelial to mesenchymal transition.
  37. (2005). TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT).
  38. (2009). The basics of epithelial-mesenchymal transition.
  39. (2007). The CD34-related molecule podocalyxin is a potent inducer of microvillus formation.
  40. (2009). The class I bHLH factors E2-2A and E2-2B regulate EMT.
  41. (2010). The human cancer and stem cell marker podocalyxin interacts with the glucose-3-transporter in malignant pluripotent stem cells.
  42. (2009). The role of podocalyxin in health and disease.
  43. (2002). The SLUG zinc-finger protein represses E-cadherin in breast cancer.
  44. (2009). Towards understanding epithelial-mesenchymal transition: A proteomics perspective.
  45. (2010). Transcriptome profiling of a TGF-beta-induced epithelial-to-mesenchymal transition reveals extracellular clusterin as a target for therapeutic antibodies.
  46. (2007). Transforming growth factor-beta and microRNA:mRNA regulatory networks in epithelial %plasticity. Cells Tissues Organs (Print)