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Published in: Journal of Translational Medicine 1/2016

Open Access 01-12-2016 | Review

p90 ribosomal S6 kinase: a potential therapeutic target in lung cancer

Authors: Noufira Poomakkoth, Aya Issa, Nabeel Abdulrahman, Somaia Gamal Abdelaziz, Fatima Mraiche

Published in: Journal of Translational Medicine | Issue 1/2016

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Abstract

A global survey of cancer has shown that lung cancer is the most common cause of the new cancer cases and cancer deaths in men worldwide. The mortality from lung cancer is more than the combined mortality from breast, prostate and colorectal cancers. The two major histological types of lung cancer are non-small cell lung cancer (NSCLC) accounting for about 85 % of cases and small cell lung cancer accounting for 15 % of cases. NSCLC, the more prevalent form of lung cancer, is often diagnosed at an advanced stage and has a very poor prognosis. Many factors have been shown to contribute to the development of lung cancer in humans including tobacco smoking, exposure to environmental carcinogens (asbestos, or radon) and genetic factors. Despite the advances in treatment, lung cancer remains one of the leading causes of cancer death worldwide. Interestingly, the overall 5 year survival from lung cancer has not changed appreciably in the past 25 years. For this reason, novel and more effective treatments and strategies for NSCLC are critically needed. p90 ribosomal S6 kinase (RSK), a serine threonine kinase that lies downstream of the Ras–MAPK (mitogen activated protein kinase) cascade, has been demonstrated to be involved in the regulation of cell proliferation in various malignancies through indirect (e.g., modulation of transcription factors) or direct effects on the cell-cycle machinery. Increased expression of RSK has been demonstrated in various cancers, including lung cancer. This review focuses on the role of RSK in lung cancer and its potential therapeutic application.
Literature
3.
go back to reference Gridelli C, Bareschino MA, Schettino C, Rossi A, Maione P, Ciardiello F. Erlotinib in non-small cell lung cancer treatment: current status and future development. Oncologist. 2007;12(7):840–9.CrossRefPubMed Gridelli C, Bareschino MA, Schettino C, Rossi A, Maione P, Ciardiello F. Erlotinib in non-small cell lung cancer treatment: current status and future development. Oncologist. 2007;12(7):840–9.CrossRefPubMed
7.
go back to reference Johnson DH, Schiller JH, Bunn PA. Recent clinical advances in lung cancer management. J Clin Oncol. 2014;32(10):973–82.CrossRefPubMed Johnson DH, Schiller JH, Bunn PA. Recent clinical advances in lung cancer management. J Clin Oncol. 2014;32(10):973–82.CrossRefPubMed
9.
go back to reference Panov SZ. Molecular biology of the lung cancer. Radiol Oncol. 2005;39(3):197–210. Panov SZ. Molecular biology of the lung cancer. Radiol Oncol. 2005;39(3):197–210.
10.
go back to reference Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 2011;11(9):671–7.CrossRefPubMed Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 2011;11(9):671–7.CrossRefPubMed
11.
go back to reference Xu F, Tian Y, Huang Y, Zhang LL, Guo ZZ, Huang JJ, Lin TY. EGFR inhibitors sensitize non small cell lung cancer cells to TRAIL apoptosis. Chin J Cancer. 2011;30(10):701–11.PubMedCentralCrossRefPubMed Xu F, Tian Y, Huang Y, Zhang LL, Guo ZZ, Huang JJ, Lin TY. EGFR inhibitors sensitize non small cell lung cancer cells to TRAIL apoptosis. Chin J Cancer. 2011;30(10):701–11.PubMedCentralCrossRefPubMed
12.
go back to reference Janmaat MLFA, Rodriguez JA, et al. Response to epidermal growth factor receptor inhibitors in non small cell lung cancer cells: limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways. Clin Cancer Res. 2003;9:2316–26.PubMed Janmaat MLFA, Rodriguez JA, et al. Response to epidermal growth factor receptor inhibitors in non small cell lung cancer cells: limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways. Clin Cancer Res. 2003;9:2316–26.PubMed
13.
go back to reference Engelman JAZK, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039–43.CrossRefPubMed Engelman JAZK, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039–43.CrossRefPubMed
14.
go back to reference Romeo Y, Zhang X, Roux PP. Regulation and function of the RSK family of protein kinases. Biochem J. 2012;441(2):553–69.CrossRefPubMed Romeo Y, Zhang X, Roux PP. Regulation and function of the RSK family of protein kinases. Biochem J. 2012;441(2):553–69.CrossRefPubMed
15.
go back to reference Vakiani E, Solit DB. KRAS and BRAF: drug targets and predictive biomarkers. J Pathol. 2011;223(2):219–29.CrossRefPubMed Vakiani E, Solit DB. KRAS and BRAF: drug targets and predictive biomarkers. J Pathol. 2011;223(2):219–29.CrossRefPubMed
17.
go back to reference Stinchombe ET, Johnson GL. MEK inhibition in non-small cell lung cancer. Lung Cancer. 2014;86(2):121–5.CrossRef Stinchombe ET, Johnson GL. MEK inhibition in non-small cell lung cancer. Lung Cancer. 2014;86(2):121–5.CrossRef
18.
go back to reference Anjum R, Blenis J. The RSK family of kinases: emerging roles in cellular signalling. Nat Rev Mol Cell Biol. 2008;9(10):747–58.CrossRefPubMed Anjum R, Blenis J. The RSK family of kinases: emerging roles in cellular signalling. Nat Rev Mol Cell Biol. 2008;9(10):747–58.CrossRefPubMed
19.
go back to reference Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005;23(25):5900–9.CrossRefPubMed Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005;23(25):5900–9.CrossRefPubMed
20.
go back to reference Lowe HIFC, Toyang NJ, Bryant JL. Specific RSK Kinase Inhibition by Dibenzyl Trisulfide and Implication for Therapeutic Treatment of Cancer. Anticancer Res. 2014;34:1637–42.PubMed Lowe HIFC, Toyang NJ, Bryant JL. Specific RSK Kinase Inhibition by Dibenzyl Trisulfide and Implication for Therapeutic Treatment of Cancer. Anticancer Res. 2014;34:1637–42.PubMed
21.
go back to reference Erikson EMJ. A protein kinase from Xenopus eggs specific for ribosomal protein S6. Proc Nati Acad Sci USA. 1985;82:742–6.CrossRef Erikson EMJ. A protein kinase from Xenopus eggs specific for ribosomal protein S6. Proc Nati Acad Sci USA. 1985;82:742–6.CrossRef
22.
go back to reference Lara R, Seckl MJ, Pardo OE. The p90 RSK family members: common functions and isoform specificity. Cancer Res. 2013;73(17):5301–8.CrossRefPubMed Lara R, Seckl MJ, Pardo OE. The p90 RSK family members: common functions and isoform specificity. Cancer Res. 2013;73(17):5301–8.CrossRefPubMed
23.
go back to reference Morten Frodin SG. Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Mol Cell Endocrinol. 1999;151:65–77.CrossRef Morten Frodin SG. Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Mol Cell Endocrinol. 1999;151:65–77.CrossRef
24.
go back to reference Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004;68(2):320–44.PubMedCentralCrossRefPubMed Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004;68(2):320–44.PubMedCentralCrossRefPubMed
25.
26.
go back to reference Anjum R, Roux PP, Ballif BA, Gygi SP, Blenis J. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Curr Biol. 2005;15(19):1762–7.CrossRefPubMed Anjum R, Roux PP, Ballif BA, Gygi SP, Blenis J. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Curr Biol. 2005;15(19):1762–7.CrossRefPubMed
27.
go back to reference Dehan E, Bassermann F, Guardavaccaro D, Vasiliver-Shamis G, Cohen M, Lowes K, Dustin M, Huang DCS, Taunton J, Pagano M. βTrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis. Mol Cell. 2009;33(1):109–16.PubMedCentralCrossRefPubMed Dehan E, Bassermann F, Guardavaccaro D, Vasiliver-Shamis G, Cohen M, Lowes K, Dustin M, Huang DCS, Taunton J, Pagano M. βTrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis. Mol Cell. 2009;33(1):109–16.PubMedCentralCrossRefPubMed
28.
go back to reference Doehn U, Hauge C, Frank SR, Jensen CJ, Duda K, Nielsen JV, et al. RSK is a principal effector of the RAS-ERK pathway for eliciting a coordinate promotile/invasive gene program and phenotype in epithelial cells. Mol Cell. 2009;35(4):511–22.PubMedCentralCrossRefPubMed Doehn U, Hauge C, Frank SR, Jensen CJ, Duda K, Nielsen JV, et al. RSK is a principal effector of the RAS-ERK pathway for eliciting a coordinate promotile/invasive gene program and phenotype in epithelial cells. Mol Cell. 2009;35(4):511–22.PubMedCentralCrossRefPubMed
30.
go back to reference Lara R, Mauri FA, Taylor H, Derua R, Shia A, Gray C, et al. An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis. Oncogene. 2011;30(32):3513–21.CrossRefPubMed Lara R, Mauri FA, Taylor H, Derua R, Shia A, Gray C, et al. An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis. Oncogene. 2011;30(32):3513–21.CrossRefPubMed
31.
go back to reference Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, et al. The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007;408(3):297–315.PubMedCentralCrossRefPubMed Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, et al. The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007;408(3):297–315.PubMedCentralCrossRefPubMed
32.
go back to reference Sapkota GP, Cummings L, Newell FS, Armstrong C, Bain J, Frodin M, et al. BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J. 2007;401(1):29–38.PubMedCentralCrossRefPubMed Sapkota GP, Cummings L, Newell FS, Armstrong C, Bain J, Frodin M, et al. BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J. 2007;401(1):29–38.PubMedCentralCrossRefPubMed
33.
go back to reference Cohen MS, Zhang C, Shokat KM, Taunton J. Structural bioinformatics-based design of selective, irreversible kinase inhibitors. Science. 2005;308(5726):1318–21.PubMedCentralCrossRefPubMed Cohen MS, Zhang C, Shokat KM, Taunton J. Structural bioinformatics-based design of selective, irreversible kinase inhibitors. Science. 2005;308(5726):1318–21.PubMedCentralCrossRefPubMed
Metadata
Title
p90 ribosomal S6 kinase: a potential therapeutic target in lung cancer
Authors
Noufira Poomakkoth
Aya Issa
Nabeel Abdulrahman
Somaia Gamal Abdelaziz
Fatima Mraiche
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2016
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-016-0768-1

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