CD26 Regulates p38 Mitogen-Activated Protein Kinase–Dependent Phosphorylation of Integrin β1, Adhesion to Extracellular Matrix, and Tumorigenicity of T-Anaplastic Large Cell Lymphoma Karpas 299

Abstract

CD26 is an antigen with key role in T-cell biology and is expressed on selected subsets of aggressive T-cell malignancies. To elucidate the role of CD26 in tumor behavior, we examine the effect of CD26 depletion by small interfering RNA transfection of T-anaplastic large cell lymphoma Karpas 299. We show that the resultant CD26-depleted clones lose the ability to adhere to fibronectin and collagen I. Because antiintegrin B 1 blocking antibodies also prevent binding of Karpas 299 to fibronectin and collagen I, we then evaluate the CD26-integrin B 1 association. CD26 depletion does not decrease integrin B 1 expression but leads to dephosphorylation of both integrin B 1 and p38 mitogen-activated protein kinase (MAPK). Moreover, our data showing that the p38MAPK inhibitor SB203580 dephosphorylates integrin B 1 and that binding of the anti-CD26 antibody 202.36 dephosphorylates both p38MAPK and integrin B 1 on Karpas 299, leading to loss of cell adhesion to the extracellular matrix, indicate that CD26 mediates cell adhesion through p38MAPK-dependent phosphorylation of integrin B 1 . Finally, in vivo experiments show that depletion of CD26 is associated with loss of tumorigenicity and greater survival. Our findings hence suggest that CD26 plays an important role in tumor development and may be a novel therapeutic target for selected neoplasms. (Cancer Res 2005; 65(15): 6950-6)

Maternal N-Carbamylglutamate Supplementation during Early Pregnancy Enhances Embryonic Survival and Development through Modulation of the Endometrial Proteome in Gilts

“…Calreticulin, a high-affinity Ca 2+ -binding protein, is essential for integrin-mediated cell adhesion to extracellular matrix by associating with the cytoplasmic domains of integrin-a subunits (36). Dipeptidyl peptidase IV has been reported to be associated with integrin-dependent adhesion by regulating MAPK-dependent phosphorylation of integrins (37). Our results indicate that NCG may enhance embryonic implantation via the integrin-mediated signaling pathway, thus decreasing the rate of embryonic losses during early pregnancy.…”

Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease

“…17 DPP IV has been shown to participate in T-cell biology as a co-stimulatory molecule able to regulate signalling transduction pathways. [18][19][20] In addition to its role in T-cell biology, DPP IV also plays an important role in the pathogenesis of kidney diseases such as IgA nephropathy. 21 We here studied the excretion of DPP IV in urinary microvesicles in a small cohort of patients with T2DM by categorising them into three groups according to the severity of kidney damage.…”

Salvicine Inactivates β1 Integrin and Inhibits Adhesion of MDA-MB-435 Cells to Fibronectin via Reactive Oxygen Species Signaling

“…A recent study reported that the p38-dependent phosphorylation of h 1 integrin at Ser 785 was critical for adhesion of the T-cell lymphoma line Karpas299 to fibronectin and collagen. However, this phenomenon was highly cell type specific (31). Other issues, however, stand quite in contrast to this case and gave a clue that p38 MAPK may inhibit h 1 integrin function (32).…”