Tags

Type your tag names separated by a space and hit enter

p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells.
J Clin Invest. 2010 Apr; 120(4):1165-77.JCI

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.

Authors+Show Affiliations

Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, USA. smkang@emory.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20234090

Citation

Kang, Sumin, et al. "P90 Ribosomal S6 Kinase 2 Promotes Invasion and Metastasis of Human Head and Neck Squamous Cell Carcinoma Cells." The Journal of Clinical Investigation, vol. 120, no. 4, 2010, pp. 1165-77.
Kang S, Elf S, Lythgoe K, et al. P90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells. J Clin Invest. 2010;120(4):1165-77.
Kang, S., Elf, S., Lythgoe, K., Hitosugi, T., Taunton, J., Zhou, W., Xiong, L., Wang, D., Muller, S., Fan, S., Sun, S. Y., Marcus, A. I., Gu, T. L., Polakiewicz, R. D., Chen, Z. G., Khuri, F. R., Shin, D. M., & Chen, J. (2010). P90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells. The Journal of Clinical Investigation, 120(4), 1165-77. https://doi.org/10.1172/JCI40582
Kang S, et al. P90 Ribosomal S6 Kinase 2 Promotes Invasion and Metastasis of Human Head and Neck Squamous Cell Carcinoma Cells. J Clin Invest. 2010;120(4):1165-77. PubMed PMID: 20234090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells. AU - Kang,Sumin, AU - Elf,Shannon, AU - Lythgoe,Katherine, AU - Hitosugi,Taro, AU - Taunton,Jack, AU - Zhou,Wei, AU - Xiong,Li, AU - Wang,Dongsheng, AU - Muller,Susan, AU - Fan,Songqing, AU - Sun,Shi-Yong, AU - Marcus,Adam I, AU - Gu,Ting-Lei, AU - Polakiewicz,Roberto D, AU - Chen,Zhuo Georgia, AU - Khuri,Fadlo R, AU - Shin,Dong M, AU - Chen,Jing, Y1 - 2010/03/15/ PY - 2009/07/21/received PY - 2010/01/13/accepted PY - 2010/3/18/entrez PY - 2010/3/18/pubmed PY - 2010/4/22/medline SP - 1165 EP - 77 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 120 IS - 4 N2 - 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. SN - 1558-8238 UR - https://www.unboundmedicine.com/medline/citation/20234090/p90_ribosomal_S6_kinase_2_promotes_invasion_and_metastasis_of_human_head_and_neck_squamous_cell_carcinoma_cells_ L2 - https://doi.org/10.1172/JCI40582 DB - PRIME DP - Unbound Medicine ER -