Epstein-Barr virus-encoded LMP2A stimulates migration of nasopharyngeal carcinoma cells via the EGFR/Ca(2+)/calpain/ITGβ4 axis

Biology Open
Jiezhen LiangXiaoying Zhou

Abstract

Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) promotes the motility of nasopharyngeal carcinoma (NPC) cells. Previously, we have shown that the localization of integrin β4 (ITGβ4) is regulated by LMP2A, with ITGβ4 concentrated at the cellular protrusions in LMP2A-expressing NPC cells. In the present study, we aim to further investigate mechanisms involved in this process and its contribution to cell motility. We show that expression of LMP2A was correlated with increased epidermal growth factor receptor (EGFR) activation, elevated levels of intracellular Ca(2+), calpain activation and accelerated cleavage of ITGβ4. Activation of EGFR and calpain activity was responsible for a redistribution of ITGβ4 from the basal layer of NPC cells to peripheral membrane structures, which correlated with an increased migratory capacity of NPC cells. Furthermore, we demonstrated that the calpain inhibitor calpastatin was downregulated in NPC primary tumors. In conclusion, our results point to LMP2A-mediated targeting of the EGFR/Ca(2+)/calpain/ITGβ4 signaling system as a mechanism underlying the increased motility of NPC cells. We suggest that calpain-facilitated cleavage of ITGβ4 contributes to the malignant phenotype of ...Continue Reading

References

Nov 3, 1995·The Journal of Biological Chemistry·X DuM H Ginsberg
May 1, 1994·Experimental Cell Research·A J PottsM E Hemler
Jul 1, 1996·The Journal of Cell Biology·F MainieroF G Giancotti
Oct 1, 1996·Molecular Membrane Biology·H Kawasaki, S Kawashima
Feb 7, 1998·The Biochemical Journal·H SorimachiK Suzuki
Nov 26, 1999·FEBS Letters·M PfaffM H Ginsberg
Oct 24, 2001·Seminars in Cancer Biology·K M Izumi
Aug 7, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Virote SriuranpongJ Silvio Gutkind
Sep 28, 2004·Nature Cell Biology·Santos J FrancoAnna Huttenlocher
Aug 29, 2006·The Journal of Biological Chemistry·Xiaodong XiXiaoping Du
Oct 25, 2006·Biochimica Et Biophysica Acta·Mounia ChamiPatrizia Paterlini-Bréchot
May 5, 2007·Expert Reviews in Molecular Medicine·Qian Tao, Anthony T C Chan
Jun 15, 2007·Expert Reviews in Molecular Medicine·Lucy R Osborne, Carolyn B Mervis
Dec 3, 2009·The FEBS Journal·Pablo Sánchez-GonzálezAntonio Villalobo
Jan 29, 2011·The Journal of Biological Chemistry·Christa L CortesioAnna Huttenlocher
Apr 2, 2011·The Journal of Biological Chemistry·Olivier DellisChristine Chomienne
Apr 22, 2011·Nature Reviews. Cancer·Sarah J StorrStewart G Martin
Dec 14, 2011·Molecular Biology of the Cell·Nina RintanenVarpu Marjomäki
Jun 8, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Zhigang HongStephen L Archer
Feb 11, 2015·The Journal of Investigative Dermatology·Kristin SeltmannThomas M Magin
Sep 1, 2015·Lancet·Melvin L K ChuaAnthony T C Chan

❮ Previous
Next ❯

Citations

Nov 30, 2018·World Journal of Gastroenterology : WJG·Carolina Rosal Teixeira de SouzaRommel Mario Rodríguez Burbano
Nov 13, 2020·Cancer Biotherapy & Radiopharmaceuticals·Guo-Sheng LiHong-Yu Wei
Jun 18, 2018·Biomaterials·A D SchwartzS R Peyton
Mar 26, 2021·International Immunopharmacology·Xiaoxu Li, Wenling Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
Fluorescence
Flow cytometry
confocal microscopy
biopsies
protein assay
electrophoresis
Assay

Software Mentioned

GraphPad Prism
Pro Plus
BD
Image
HiPic
FACSDiva

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.