Jak3 is involved in CCR7-dependent migration and invasion in metastatic squamous cell carcinoma of the head and neck

Abstract

Abstract. Patients with cervical lymph node metastasis in squamous cell carcinoma of the head and neck (SCCHN) exhibit a poor prognosis and low 5-year survival rate. It has been proven that chemokine receptor 7 (CCR7) promotes cellular migration and invasion in metastatic SCCHN. In the present study, the metastatic SCCHN PCI-37B cell line was utilized to explore the role of Janus activated kinase-3 (Jak3) in the CCR7-mediated signaling pathway in metastatic SCCHN cells. It was observed that phospho-Jak3 was expressed in SCCHN tissues. In addition, when the PCI-37B cells were analyzed in response to chemokine ligand 19 (CCL19), the ligand of CCR7, at the indicated time points, the results of the present study demonstrated that CCR7 induced Jak3 activation, and inhibition of Jak3 activity using a specific inhibitor, ZM39923, significantly attenuated CCR7-induced Jak3 phosphorylation. Migration and invasion assays and immunofluorescence staining experiments demonstrated that CCL19 promoted cell migration, invasion and F-actin rearrangment in CCR7-expressing SCCHN cells partially due to the activation of the Jak3 signaling pathway. These results demonstrate that the Jak3 signaling pathway is important for the CCR7-induced malignant biological behavior of SCCHN cells.

Prognostic value of immunoexpression of CCR4, CCR5, CCR7 and CXCR4 in squamous cell carcinoma of tongue and floor of the mouth

“…Previous research reported that CCR7 regulate metastasis in head and neck SCC (28,33,34,35). The importance of the signaling way Janus activated kinase-3 (Jak3) in the metastasis of malignant head and neck tumors mediated by CCR7 and its ligands, can be a new target for treatment of these patients (36). Also, was reported that CCR7 can activate JAK2/STAT3 and to promote metastasis.…”

CCR7 as a therapeutic target in Cancer

“…CCR7 belong to the GPCR family and it is already known that activation of GPCRs can stimulate a number of intracellular signalling pathways. Indeed, binding of CCL19 or CCL21 to CCR7 is shown to result in activation of intracellular signalling pathways in tumour cell including PI3/akt [221][222][223], MAPK/ERK [161,[224][225][226][227], and Jak/STAT [228,229] pathways (Figure 1). Through modulation of these intracellular pathways, the CCR7 axis can exert a multifaceted influence on the biology of the cell and in particular have involvements in metastasis which goes J o u r n a l P r e -p r o o f beyond directing the migration.…”

Therapeutic siRNAs Targeting the JAK/STAT Signalling Pathway in Inflammatory Bowel Diseases

“… 49 Developing new therapeutics highly specific to either JAK1 or JAK3 could be greatly beneficial for patients with cancer and immune-related diseases, or even infections. Indeed, JAK1 and JAK3 have been widely described as potential therapeutic targets for several types of cancer, including gliomas, 50 , 51 head and neck cancers and oesophageal squamous cell carcinoma, 52 , 53 , 54 , 55 breast cancer, 56 , 57 multiple myeloma, 58 , 59 colon cancer 60 , 61 and pancreatic cancer, 62–64 as well as for developing cancer immunotherapies. 65 JAK3 has been particularly highlighted as a therapeutic target in immune cell-related cancers, including B-lineage acute lymphoblastic leukaemia 66 and natural killer/T-cell lymphoma, 67 and also for improving allotransplantation.…”