p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells

• Type of Material: Article
• Authors: Sumin Kang, Emory University; Shannon Elf, Emory University; Katherine Lythgoe, Emory University; Taro Hitosugi, Emory University; Jack Taunton, Emory University; Wei Zhou, Emory University; Li Xiong, Emory University; Dongsheng Wang, Emory University; Susan Muller, Emory University; Songqing Fan, Emory University; Shi-Yong Sun, Emory University; Adam I Marcus, Emory University; Ting-Lei Gu, Emory University; Roberto D. Polakiewicz, Emory University; Georgia Chen, Emory University; Fadlo Khuri, Emory University; Dong M Shin, Emory University; Jing Chen, Emory University
• Language: English
• Date: 2010-04-01
• Publisher: American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2010, American Society for Clinical Investigation
• Final Published Version (URL): http://mcb.asm.org/content/33/13/2574.full
• Title of Journal or Parent Work: Journal of Clinical Investigation
• ISSN: 0021-9738
• Volume: 120
• Issue: 4
• Start Page: 1165
• End Page: 1177
• Grant/Funding Information: J. Chen, S.-Y. Sun, Z.G. Chen, F.R. Khuri, and D.M. Shin are Georgia Cancer Coalition Distinguished Cancer Scholars.; J. Chen is an American Cancer Society Basic Research Scholar.; S. Kang is a Special Fellow of the Leukemia and Lymphoma Society.; This work was supported in part by NIH grant CA120272 (to J. Chen) and Head and Neck Cancer SPORE grant P50CA128613 (to S. Kang, S. Muller, S.-Y. Sun, Z.G. Chen, F.R. Khuri, D.M. Shin, and J. Chen).
• Research Categories: Health Sciences, Oncology; Health Sciences, Pharmacology

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of human cancer and frequently metastasizes to LNs. Identifying metastasis-promoting factors is of immense clinical interest, as the prognosis for patients with even a single unilateral LN metastasis is extremely poor. Here, we report that p90 ribosomal S6 kinase 2 (RSK2) promotes human HNSCC cell invasion and metastasis. We determined that RSK2 was overexpressed and activated in highly invasive HNSCC cell lines compared with poorly invasive cell lines. Expression of RSK2 also correlated with metastatic progression in patients with HNSCC. Ectopic expression of RSK2 substantially enhanced the invasive capacity of HNSCC cells, while inhibition of RSK2 activity led to marked attenuation of invasion in vitro. Additionally, shRNA knockdown of RSK2 substantially reduced the invasive and metastatic potential of HNSCC cells in vitro and in vivo in a xenograft mouse model, respectively. Mechanistically, we determined that cAMP-responsive element-binding protein (CREB) and Hsp27 are phosphorylated and activated by RSK2 and are important for the RSK2-mediated invasive ability of HNSCC cells. Our findings suggest that RSK2 is involved in the prometastatic programming of HNSCC cells, through phosphorylation of proteins in a putative signaling network. Moreover, targeting RSK2 markedly attenuates in vitro invasion and in vivo metastasis of HNSCC cells, suggesting that RSK2 may represent a therapeutic target in the treatment of metastatic HNSCC.