Syntaxins 3 and 4 mediate vesicular trafficking of α5β1 and α3β1 integrins and cancer cell migration

  • Authors: Paul Day, Krista A. Riggs, Nazarul Hasan, Deborah Corbin, David Humphrey, Chuan Hu
  • View Affiliations

  • Published online on: Tuesday, June 28, 2011
  • Pages: 863-871
  • DOI: 10.3892/ijo.2011.1101

Abstract

Integrins, a family of heterodimeric receptors for cell adhesion to the extracellular matrix (ECM), play key roles in cell migration, cancer progression and metastasis. As transmembrane proteins, integrins are transported in vesicles and delivered to the cell surface by vesicular trafficking. The final step for integrin delivery, i.e., fusion of integrin-containing vesicles with the plasma membrane, is poorly understood at the molecular level. The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins syntaxins 1, 2, 3 and 4 are present at the plasma membrane to drive vesicle fusion. In this study, we examined the roles of syntaxins 1, 2, 3 and 4 in vesicular trafficking of α5β1 and α3β1 integrins. We showed that syntaxins 2, 3 and 4 were expressed in HeLa cervical adenocarcinoma cells and PANC-1 pancreatic adenocarcinoma cells. In migrating HeLa and PANC-1 cells, syntaxins 2, 3 and 4 co-localized with the lipid raft constituent GM1 ganglioside at the leading edge. siRNA knockdown (KD) of syntaxins 3 and 4, but not of syntaxin 2, in HeLa cells reduced cell surface expression of α5β1 and α3β1 integrins and accumulated the integrins in cytoplasmic vesicles, indicating that syntaxins 3 and 4 mediate vesicular trafficking of α5β1 and α3β1 integrins to the cell surface. In addition, KD of syntaxins 3 and 4 inhibited cell adhesion to fibronectin, suppressed chemotactic cell migration and triggered apoptosis. Collectively, these data suggest that syntaxins 3- and 4-dependent integrin trafficking is important in cancer cell migration and survival, and may be a valuable target for cancer therapy.
Journal Cover

October 2011
Volume 39 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Day, P., Riggs, K., Hasan, N., Corbin, D., Humphrey, D., & Hu, C. (2011). Syntaxins 3 and 4 mediate vesicular trafficking of α5β1 and α3β1 integrins and cancer cell migration. International Journal of Oncology, 39(4), 863-871.
MLA
Day, Riggs, Hasan, Corbin, Humphrey, and Chuan Hu. "Syntaxins 3 and 4 mediate vesicular trafficking of α5β1 and α3β1 integrins and cancer cell migration." International Journal of Oncology International Journal of Oncology 39.4 (2011): 863-871.
Chicago
Day, Riggs, Hasan, Corbin, Humphrey, and Chuan Hu. "Syntaxins 3 and 4 mediate vesicular trafficking of α5β1 and α3β1 integrins and cancer cell migration." International Journal of Oncology International Journal of Oncology 39 no. 4 (2011): 863-871.