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

Sumin Kang, Shannon Elf, Katherine Lythgoe, Taro D Hitosugi, Jack Taunton, Wei Zhou, Li Xiong, Dongsheng Wang, Susan Muller, Songqing Fan, Shi Yong Sun, Adam I. Marcus, Ting Lei Gu, Roberto D. Polakiewicz, Zhuo Chen, Fadlo R. Khuri, Dong M. Shin, Jing Chen

Research output: Contribution to journalArticle

107 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1165-1177
Number of pages13
JournalJournal of Clinical Investigation
Volume120
Issue number4
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

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90-kDa Ribosomal Protein S6 Kinases
Neoplasm Metastasis
Carcinoma, squamous cell of head and neck
ribosomal protein S6 kinase, 90kDa, polypeptide 3
Cell Line
Heterografts
Small Interfering RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells. / Kang, Sumin; Elf, Shannon; Lythgoe, Katherine; Hitosugi, Taro D; Taunton, Jack; Zhou, Wei; Xiong, Li; Wang, Dongsheng; Muller, Susan; Fan, Songqing; Sun, Shi Yong; Marcus, Adam I.; Gu, Ting Lei; Polakiewicz, Roberto D.; Chen, Zhuo; Khuri, Fadlo R.; Shin, Dong M.; Chen, Jing.

In: Journal of Clinical Investigation, Vol. 120, No. 4, 01.04.2010, p. 1165-1177.

Research output: Contribution to journalArticle

Kang, S, Elf, S, Lythgoe, K, Hitosugi, TD, Taunton, J, Zhou, W, Xiong, L, Wang, D, Muller, S, Fan, S, Sun, SY, Marcus, AI, Gu, TL, Polakiewicz, RD, Chen, Z, Khuri, FR, Shin, DM & Chen, J 2010, 'p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells', Journal of Clinical Investigation, vol. 120, no. 4, pp. 1165-1177. https://doi.org/10.1172/JCI40582
Kang, Sumin ; Elf, Shannon ; Lythgoe, Katherine ; Hitosugi, Taro D ; Taunton, Jack ; Zhou, Wei ; Xiong, Li ; Wang, Dongsheng ; Muller, Susan ; Fan, Songqing ; Sun, Shi Yong ; Marcus, Adam I. ; Gu, Ting Lei ; Polakiewicz, Roberto D. ; Chen, Zhuo ; Khuri, Fadlo R. ; Shin, Dong M. ; Chen, Jing. / p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells. In: Journal of Clinical Investigation. 2010 ; Vol. 120, No. 4. pp. 1165-1177.
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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 D

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

AU - Khuri, Fadlo R.

AU - Shin, Dong M.

AU - Chen, Jing

PY - 2010/4/1

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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.

AB - 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.

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