Chemokine receptor 7 via proline-rich tyrosine kinase-2 upregulates the chemotaxis and migration ability of squamous cell carcinoma of the head and neck

Yang,Liangliang; Liu,Fayu; Xu,Zhongfei; Guo,Nan; Zheng,Xiaojiao; Sun,Changfu

doi:10.3892/or.2012.1989

Chemokine receptor 7 via proline-rich tyrosine kinase-2 upregulates the chemotaxis and migration ability of squamous cell carcinoma of the head and neck

Authors:
- Liangliang Yang
- Fayu Liu
- Zhongfei Xu
- Nan Guo
- Xiaojiao Zheng
- Changfu Sun
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Affiliations: Department of Oromaxillofacial-Head and Neck Surgery, Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China
Published online on: August 23, 2012 https://doi.org/10.3892/or.2012.1989
Pages: 1659-1664

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Abstract

Aberrant regulation in the chemotaxis and migration ability of cancer cells is closely associated with their metastatic activity. The chemokine receptor 7 (CCR7) has recently been shown to play an important role in regional lymph node metastasis of squamous cell carcinoma of the head and neck (SCCHN). In this study, we examined the role of proline-rich tyrosine kinase-2 (Pyk2) in CCR7-induced chemotaxis and migration ability of metastatic SCCHN cells. We showed that Pyk2 is overexpressed in squamous cell carcinoma of the head and neck. We also found that CCR7 induced Pyk2 and cofilin activation. Inhibition of Pyk2 activity using a pharmacological inhibitor, Tyrphostin A9, significantly attenuated CCR7-induced Pyk2 tyrosine phosphorylation, activation of cofilin and sequentially abolished F-actin rearrangment, diminished the chemotaxis and migration ability of SCCHN cells. In summary, our data suggest that CCR7 via Pyk2 and cofilin regulates the chemotaxis and migration ability of metastatic SCCHN cells.

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1	Greenlee RT, Hill-Harmon MB, Murray T and Thun M: Cancer Statistics, 2001. CA Cancer J Clin. 51:15–36. 2001. View Article : Google Scholar
2	Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, et al: Involvement of chemokine receptors in breast cancer metastasis. Nature. 410:50–56. 2001.PubMed/NCBI
3	Ben-Baruch A: Site-specific metastasis formation: chemokines as regulators of tumor cell adhesion, motility and invasion. Cell Adh Migr. 3:328–333. 2009. View Article : Google Scholar : PubMed/NCBI
4	Wang J, Xi L, Hunt JL, Gooding W, Whiteside TL, Chen Z, Godfrey TE and Ferris RL: Expression pattern of chemokine receptor 6 (CCR6) and CCR7 in squamous cell carcinoma of the head and neck identifies a novel metastatic phenotype. Cancer Res. 64:1861–1866. 2004. View Article : Google Scholar : PubMed/NCBI
5	Zhao ZJ, Liu FY, Li P, Ding X, Zong ZH and Sun CF: CCL19-induced chemokine receptor 7 activates the phosphoinositide-3 kinase-mediated invasive pathway through Cdc42 in metastatic squamous cell carcinoma of the head and neck. Oncol Rep. 25:729–737. 2011.PubMed/NCBI
6	Liu FY, Zhao ZJ, Li P, Ding X, Zong ZH and Sun CF: Mammalian target of rapamycin (mTOR) is involved in the survival of cells mediated by chemokine receptor 7 through PI3K/Akt in metastatic squamous cell carcinoma of the head and neck. Br J Oral Maxillofac Surg. 48:291–296. 2010. View Article : Google Scholar : PubMed/NCBI
7	Zhen-Jin Z, Peng L, Fa-Yu L, Liyan S and Chang-Fu S: PKCα take part in CCR7/NF-κB autocrine signaling loop in CCR7-positive squamous cell carcinoma of head and neck. Mol Cell Biochem. 357:181–187. 2011.
8	Park SY, Li H and Avraham S: RAFTK/Pyk2 regulates EGF-induced PC12 cell spreading and movement. Cell Signal. 19:289–300. 2007. View Article : Google Scholar : PubMed/NCBI
9	Picascia A, Stanzione R, Chieffi P, Kisslinger A, Dikic I and Tramontano D: Proline-rich tyrosine kinase 2 regulates proliferation and differentiation of prostate cells. Mol Cell Endocrinol. 186:81–87. 2002. View Article : Google Scholar : PubMed/NCBI
10	Kuwabara K, Nakaoka T, Sato K, Nishishita T, Sasaki T and Yamashita N: Differential regulation of cell migration and proliferation through proline-rich tyrosine kinase 2 in endothelial cells. Endocrinology. 145:3324–3330. 2004. View Article : Google Scholar : PubMed/NCBI
11	Roelle S, Grosse R, Buech T, Chubanov V and Gudermann T: Essential role of Pyk2 and Src kinase activation in neuropeptide-induced proliferation of small cell lung cancer cells. Oncogene. 27:1737–1748. 2008. View Article : Google Scholar : PubMed/NCBI
12	de Amicis F, Lanzino M, Kisslinger A, Calì G, Chieffi P, Andò S, Mancini FP and Tramontano D: Loss of proline-rich tyrosine kinase 2 function induces spreading and motility of epithelial prostate cells. Cell Physiol. 209:74–80. 2006.PubMed/NCBI
13	Behmoaram E, Bijian K, Jie S, Xu Y, Darnel A, Bismar TA and Alaoui-Jamali MA: Focal adhesion kinase-related proline-rich tyrosine kinase 2 and focal adhesion kinase are co-overexpressed in early-stage and invasive ErbB-2-positive breast cancer and cooperate for breast cancer cell tumorigenesis and invasiveness. Am J Pathol. 173:1540–1550. 2008. View Article : Google Scholar : PubMed/NCBI
14	Riol-Blanco L, Sánchez-Sánchez N, Torres A, Tejedor A, Narumiya S, Corbí AL, Sánchez-Mateos P and Rodríguez-Fernández JL: The chemokine receptor CCR7 activates in dendritic cells two signaling modules that independently regulate chemotaxis and migratory speed. J Immunol. 174:4070–4080. 2005. View Article : Google Scholar : PubMed/NCBI
15	Wang J, Zhang X, Thomas SM, Grandis JR, Wells A, Chen ZG and Ferris RL: Chemokine receptor 7 activates phosphoinositide-3 kinase-mediated invasive and prosurvival pathways in head and neck cancer cells independent of EGFR. Oncogene. 24:5897–5904. 2005. View Article : Google Scholar : PubMed/NCBI
16	Liu FY, Zhao ZJ, Li P, Ding X, Guo N, Yang LL, Zong ZH and Sun CF: NF-κB participates in chemokine receptor 7-mediated cell survival in metastatic squamous cell carcinoma of the head and neck. Oncol Rep. 25:383–391. 2011.
17	Li P, Zhao ZJ, Liu FY, Sun LY, Ding X, Zhang WZ, Shang DH and Sun CF: The chemokine receptor 7 regulates cell adhesion and migration via β1 integrin in metastatic squamous cell carcinoma of the head and neck. Oncol Rep. 24:989–995. 2010.
18	Li P, Liu F, Sun L, Zhao Z, Ding X, Shang D, Xu Z and Sun C: Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvβ3. Int J Mol Med. 27:679–687. 2011.PubMed/NCBI
19	Yuan TC, Lin FF and Veeramani S: ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells. Oncogene. 26:7552–7559. 2007. View Article : Google Scholar : PubMed/NCBI
20	Zhang S, Guo D, Jiang L, Zhang Q, Qiu X and Wang E: SOCS3 inhibiting migration of A549 cells correlates with PYK2 signaling in vitro. BMC Cancer. 28:1502008. View Article : Google Scholar : PubMed/NCBI
21	Prasad A, Fernandis AZ, Rao Y and Ganju RK: Slit protein-mediated inhibition of CXCR4-induced chemotactic and chemoinvasive signaling pathways in breast cancer cells. J Biol Chem. 279:9115–924. 2004. View Article : Google Scholar : PubMed/NCBI
22	Fernandis AZ, Prasad A, Band H, Klösel R and Ganju RK: Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells. Oncogene. 23:157–167. 2004. View Article : Google Scholar : PubMed/NCBI
23	Ostergaard HL and Lysechko TL: Focal adhesion kinase-related protein tyrosine kinase Pyk2 in T-cell activation and function. Immunol Res. 31:267–282. 2005. View Article : Google Scholar : PubMed/NCBI
24	Gismondi A, Jacobelli J, Strippoli R, Mainiero F, Soriani A, Cifaldi L, Piccoli M, Frati L and Santoni A: Proline-rich tyrosine kinase 2 and Rac activation by chemokine and integrin receptors controls NK cell transendothelial migration. J Immunol. 170:3065–3073. 2003. View Article : Google Scholar : PubMed/NCBI
25	Oser M and Condeelis J: The cofilin activity cycle in lamellipodia and invadopodia. J Cell Biochem. 108:1252–1262. 2009. View Article : Google Scholar : PubMed/NCBI
26	van Rheenen J, Condeelis J and Glogauer M: A common cofilin activity cycle in invasive tumor cells and inflammatory cells. J Cell Sci. 122:305–311. 2009.PubMed/NCBI
27	Pollard TD and Borisy GG: Cellular motility driven by assembly and disassembly of actin filaments. Cell. 112:453–465. 2003. View Article : Google Scholar : PubMed/NCBI
28	Sun CK, Ng KT, Lim ZX, Cheng Q, Lo CM, Poon RT, Man K, Wong N and Fan ST: Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition. PLoS One. 6:e188782011. View Article : Google Scholar : PubMed/NCBI