The role of Pyk2 in the CCR7-mediated regulation of metastasis and viability in squamous cell carcinoma of the head and neck cells in vivo and in vitro

Abstract

In the present study, we aimed to demonstrate whether praline-rich tyrosine kinase-2 (Pyk2) participates in the chemokine receptor 7 (CCR7) downstream signaling network, and to determine the role of this molecule and the related mechanism in the CCR7-mediated regulation of viability and metastasis in vivo and in vitro of squamous cell carcinoma of the head and neck (SCCHN). We constructed the stable Pyk2 related non-kinase (PRNK)-expressing SCCHN cell line, and examined the viability, apoptosis, migration, invasion and adhesion ability in the transfected and untransfected SCCHN cells. An SCCHN tumor model in nude mice was designed and the tumor growth rate was assayed. E-cadherin and vimentin expression was assessed when Pyk2 was inactivated. We found that the stable PRNK-expressing SCCHN cells exhibited low viability, a high rate of apoptosis, low migratory ability, low invasive ability and low adhesion capacity. In the nude mouse body, the tumors formed by these cells grew slowly when compared to the tumor growth in the control group. When Pyk2 was inactivated, CCR7-induced E-cadherin and vimentin expression levels were altered. Thus, Pyk2 is a key downstream signaling molecules of CCR7 in SCCHN, which promotes SCCHN tumorigenesis and progression.

Proline-Rich Protein Tyrosine Kinase 2 in Inflammation and Cancer

“…Macrophages treated with a cell permeable TAT fusion protein containing the C-terminus of Pyk2 (TAT-PRNK) showed significantly impaired CD11b/CD18-mediated phagocytosis [ 16 ]. Stable PRNK-expressing squamous carcinoma cells exhibited low viability, low migratory ability, low invasive ability and low adhesion capacity [ 17 ]. PRNK does not interact with the Pyk2 partner p130 Cas or Graf, suggesting that its capacity to act as an endogenous regulator of Pyk2 may be restricted to certain cell types [ 12 ].…”

Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis

“…For example, the DEXD/H box helicase 60 ( DDX60 ) gene, a known regulator of the antiviral response and a DNA‐/RNA‐binding protein, has been reported to be associated with the development and prognosis of squamous cell carcinoma (Fu et al ., ). Similarly, PTK2B has been reported to be involved in the CCR7‐mediated regulation of metastasis in squamous cell carcinoma (Yue et al ., ) and was found to be downregulated in our study.…”

“…Histamine has been shown to play an important role in immune cell function (Hansson et al, 1999), and a histamine/IL-2 combination has been used to increase T-cell responses in stage IV melanoma patients (Asemissen et al, 2005). In addition to the five genes mentioned above, an additional nine genes (CCBE1, GPX3, PTK2B, LSP1, DDX60, PARP14, GABRE, JUP and MID1) have been associated with metastasis in other types of epithelial or solid cancers (Aktary and Pasdar, 2013;Bachmann et al, 2014;Hao et al, 2010;Jeltsch et al, 2014;Koral et al, 2015;Yue et al, 2015;Zhang et al, 2014b).…”

Novel Molecular Targets for Chemoprevention in Malignancies of the Head and Neck

“…Yang et al reported that praline-rich tyrosine kinase 2 (Pyk-2) is activated when CCR7 binds with its ligand CCL19 in SCCHN cells [ 91 ]. The same group of authors then demonstrated that Pyk-2 acts as an important downstream signaling player of the CCR7 pathway in SCCHN by regulating CCL19 dependent tumor cell migration, metastasis and viability [ 92 ]. Monoclonal antibodies targeting chemokine receptors are being tested in clinical trials against a variety of cancer types, particularly lymphomas and leukemias [ 93 ].…”