+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes

, : EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes. American Journal of Physiology. Gastrointestinal and Liver Physiology 287(6): G1227-G1237

The epidermal growth factor receptor ( EGFR) activates several signaling cascades in response to epidermal growth factor stimulation. One of these signaling events involves tyrosine phosphorylation of signal transducer and activator of transcription ( STAT), whereas another involves activation of the phosphatidylinositol 3-OH kinase pathway. Two possibilities for STAT activation exist: a janus kinase (JAK)-dependent and a JAK-independent mechanism. Herein, we demonstrate that EGFR overexpression in primary esophageal keratinocytes activates STAT in a JAK-dependent fashion with the functional consequence of enhanced cell migration, which can be abolished by use of a JAK-specific inhibitor, AG-490. We determined the mechanisms underlying the signal transduction pathway responsible for increased cell migration. Stimulation of EGFR induces Tyr701 phosphorylation of STAT1 and initiates complex formation of STAT1 and STAT3 with JAK1 and JAK2. Thereafter, the STATs translocate to the nucleus within 15 min. In addition, we found that activation of this signaling pathway results in matrix metalloproteinase-1 (MMP-1) activity. By contrast, Akt activation does not impact the EGFR-STATs-JAKs complex formation and nuclear translocation of the STATs with subsequent MMP-1 activity, although Akt activation may contribute to cell migration through an independent mechanism. Taken together, we find that the recruitment of the STAT-JAK complex by EGFR is responsible for keratinocyte migration that, in turn, might be mediated by MMP-1 activation.


PMID: 15284024

DOI: 10.1152/ajpgi.00253.2004

Other references

Duché, D.J.; Bousquet, M., 1973: Treatment of sleep disorders in children. Revue de L'infirmiere 23(2): 119-121

Rougoor, C.W.; Zeijts, H. van; Hofreither, M.F.; Backman, S., 2001: Experiences with fertilizer taxes in Europe. A levy on nitrogen fertilizer is evaluated, using real life experiences in Austria, Finland and Sweden until 1995. In these countries such a levy system was introduced in 1986, 1976 and 1985, respectively. Rates varied from between 10% and 72% of...

Dreistadt S.H.; Dahlsten D.L., 1990: Distribution and abundance of erynniopsis antennata diptera tachinidae and tetrastichus brevistigma hymenoptera eulophidae two introduced elm leaf beetle parasitoids in northern california usa. Eryniopsis antennata (Rondani), an introduced larval and larval-adult parasitoid of the elm leaf beetle (ELB). Xanthogaleruca luteola (Mueller), was found in 11 of 12 northern California cities where Ulmus pocera Salisbury and Ulmus pumila L. were...

Marcheix, B.; Demers, P.; Vanden Eynden, Fédéric.; Lamarche, Y.; Therasse, E.; Cartier, R., 2007: Alternative approach for stent grafting of the thoracic descending aorta: the antegrade right axillary approach. Journal of Thoracic and Cardiovascular Surgery 133(6): 1639-1641

Jeong, Sueng Won, 2013: The viscosity of fine-grained sediments A comparison of low- to medium-activity and high-activity clays. Viscosity is generally recognized as an indicator of landslide mobilization. Viscous behavior at relatively low (high) shear rates is an important predictor of the motion of slow- (fast)-moving landslides. The viscosity in a modified Bingham model...

Van Hoepen, E.C.N., 1920: Description of some cretaceous ammonites from Pondoland. Annvaal Mus. Pretoria: 142-147

Hart, F.Dudley, 1965: Indomethacin suppositories for arthritis. Brit Med J: 421

Fort, N., 2003: Education of children and adolescents with bladder disorders. Soins; la Revue de Reference Infirmiere: 48-49

Desaulniers, D.M.; Lussier, J.G.; Goff, A.K.; Bousquet, D.; Guilbault, L.A., 1995: Follicular development and reproductive endocrinology during a synchronized estrous cycle in heifers and mature cows displaying contrasting superovulatory responses. Ovarian follicular development and plasma concentrations of progesterone (P4), estradiol-17-beta (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were compared during a synchronized estrous cycle between heifers and mature co...

Kano, T.; Miyagawa, H.; Muto, Y.; Takahashi, Y., 1980: Response of plasma cyclic AMP to exogenous glucagon in patients with severe hepatic damage (author's transl. Nihon Shokakibyo Gakkai Zasshi 77(2): 195-205