nach oben

Journal of Neuro-Oncology

Erschienen in:

29.11.2016 | Laboratory Investigation

Elevated levels of p-Mnk1, p-eIF4E and p-p70S6K proteins are associated with tumor recurrence and poor prognosis in astrocytomas

verfasst von: Weibing Fan, Weiyuan Wang, Xinfa Mao, Shuzhou Chu, Juan Feng, Desheng Xiao, Jianhua Zhou, Songqing Fan

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

Abstract

Malignant astrocytomas are able to invade neighboring and distant areas of the normal brain. Signaling pathway alterations play important role in the development of astrocytomas. Deregulation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 directly or PI3K/mTOR/S6K pathway indirectly has a critical effect on promoting cellular proliferation, malignant transformation and metastasis. We examined and analyzed the correlation between expression of p-Mnk1, p-eIF4E and p-p70S6K proteins and clinicopathological features in 103 astrocytomas and 54 non-tumorous brain tissues. The results indicated that positive percentage of overexpression of p-Mnk1 and p-eIF4E proteins in astrocytomas were significantly higher than that of in the non-tumorous brain tissues (P < 0.05). Elevated p-Mnk1 and p-eIF4E and co-overexpressed three proteins were associated with tumor recurrence (P = 0.003, P = 0.006, P = 0.007, respectively). Overexpressed p-eIF4E significantly correlated with the tumor size (P = 0.019). In addition, overexpression of p-eIF4E and three proteins common expression were related to the WHO grade of astrocytomas (P = 0.001, P = 0.044 respectively). Spearman’s rank correlation test further showed that the expression of p-Mnk1 was strongly positive correlated with the expression of p-eIF4E in astrocytomas (r = 0.294, P = 0.003). Besides, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins were inversely correlated with overall survival rates of astrocytomas. Multivariate Cox regression analysis further identified that the elevated p-eIF4E expression, three proteins common expression were correlated with unfavorable prognosis of astrocytomas regardless of ages and WHO grades. Taken together, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins could be used as novel independent poor prognostic biomarkers for patients with astrocytomas.

Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507CrossRefPubMed

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109CrossRefPubMedPubMedCentral

Gabayan AJ, Green SB, Sanan A, Jenrette J, Schultz C, Papagikos M et al (2006) GliaSite brachytherapy for treatment of recurrent malignant gliomas: a retrospective multi-institutional analysis. Neurosurgery 58(4):701–709CrossRef

Rhoads RE (1988) Cap recognition and the entry of mRNA into the protein synthesis initiation cycle. Trends Biochem Sci 13(2):52–56CrossRefPubMed

Jia Y, Polunovsky V, Bitterman PB, Wagner CR (2012) Cap-dependent translation initiation factor eIF4E: an emerging anticancer drug target. Med Res Rev 32(4):786–814CrossRefPubMed

Bitterman PB, Polunovsky VA (2012) Attacking a nexus of the oncogenic circuitry by reversing aberrant eIF4F-mediated translation. Mol Cancer Ther 11(5):1051–1061CrossRefPubMedPubMedCentral

De Benedetti A, Graff JR (2004) eIF-4E expression and its role in malignancies and metastases. Oncogene 23(18):3189–3199CrossRefPubMed

Culjkovic B, Topisirovic I, Borden KL (2007) Controlling gene expression through RNA regulons: the role of the eukaryotic translation initiation factor eIF4E. Cell Cycle 6(1):65–69CrossRefPubMed

Jauch R, Jäkel S, Netter C, Schreiter K, Aicher B, Jäckle H, Wahl MC (2005) Crystal structures of the Mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site. Structure 13(10):1559–1568CrossRefPubMed

10.

Waskiewicz AJ, Flynn A, Proud CG, Cooper JA (1997) Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J 16(8):1909–1920CrossRefPubMedPubMedCentral

11.

Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N (1999) Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. EMBO J 18(1):270–279CrossRef

12.

Shveygert M, Kaiser C, Bradrick SS, Gromeier M (2010) Regulation of eukaryotic initiation factor 4E (eIF4E) phosphorylation by mitogen-activated protein kinase occurs through modulation of Mnk1-eIF4G interaction. Mol Cell Biol 30(21):5160–5167CrossRefPubMedPubMedCentral

13.

Raught B, Gingras AC (1999) eIF4E activity is regulated at multiple levels. Int J Biochem Cell Biol 31(1):43–57CrossRefPubMed

14.

Magnuson B, Ekim B, Fingar DC (2012) Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem J 441(1):1–21CrossRefPubMed

15.

Dennis MD, Jefferson LS, Kimball SR (2012) Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis. J Biol Chem 287(51):42890–42899CrossRefPubMedPubMedCentral

16.

Wang W, Wen Q, Xu L, Xie G, Li J, Luo J et al (2014) Activation of Akt/mTOR pathway is associated with poor prognosis of nasopharyngeal carcinoma. PLoS One 9(8):e106098CrossRefPubMedPubMedCentral

17.

Zheng J, Li J, Xu L, Xie G, Wen Q, Luo J et al (2014) Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma. PLoS One 9(2):e89220CrossRefPubMedPubMedCentral

18.

Hay N (2010) Mnk earmarks eIF4E for cancer therapy. Proc Natl Acad Sci USA 107(32):13975–13976CrossRefPubMedPubMedCentral

19.

Graff JR, Konicek BW, Carter JH, Marcusson EG (2008) Targeting the eukaryotic translation initiation factor 4E for cancer therapy. Cancer Res 68(3):631–634CrossRefPubMed

20.

Fan S, Ramalingam SS, Kauh J, Xu Z, Khuri FR, Sun SY (2009) Phosphorylated eukaryotic translation initiation factor 4 (eIF4E) is elevated in human cancer tissues. Cancer Biol Ther 8(15):1463–1469CrossRefPubMedPubMedCentral

21.

Li S, Fu J, Lu C, Mapara MY, Raza S, Hengst U, Lentzsch S (2016) Elevated translation initiation factor eIF4E is an attractive therapeutic target in multiple myeloma. Mol Cancer Ther 15(4):711–719CrossRefPubMed

22.

Zhou FF, Yan M, Guo GF, Wang F, Qiu HJ, Zheng FM et al (2011) Knockdown of eIF4E suppresses cell growth and migration, enhances chemosensitivity and correlates with increase in Bax/Bcl-2 ratio in triple-negative breast cancer cells. Med Oncol 28(4):1302–1307CrossRefPubMed

23.

Soni A, Akcakanat A, Singh G, Luyimbazi D, Zheng Y, Kim D et al (2008) eIF4E knockdown decreases breast cancer cell growth without activating Akt signaling. Mol Cancer Ther 7(7):1782–1788CrossRefPubMedPubMedCentral

24.

Dong K, Wang R, Wang X, Lin F, Shen JJ, Gao P, Zhang HZ (2009) Tumor-specific RNAi targeting eIF4E suppresses tumor growth, induces apoptosis and enhances cisplatin cytotoxicity in human breast carcinoma cells. Breast Cancer Res Treat 113(3):443–456CrossRefPubMed

25.

Restuccia DF, Hemmings BA (2010) From man to mouse and back again: advances in defining tumor AKTivities in vivo. Dis Model Mech 3(11–12):705–720CrossRefPubMed

26.

Riemenschneider MJ, Betensky RA, Pasedag SM, Louis DN (2006) AKT activation in human glioblastomas enhances proliferation via TSC2 and S6 kinase signaling. Cancer Res 66(11):5618–5623CrossRefPubMed

27.

Pópulo H, Lopes JM, Soares P (2012) The mTOR signalling pathway in human cancer. Int J Mol Sci 13(2):1886–1918CrossRefPubMedPubMedCentral

28.

Holland EC, Sonenberg N, Pandolfi PP, Thomas G (2004) Signaling control of mRNA translation in cancer pathogenesis. Oncogene 23(18):3138–3144CrossRefPubMed

29.

Wendel HG, Silva RL, Malina A, Mills JR, Zhu H, Ueda T et al (2007) Dissecting eIF4E action in tumorigenesis. Genes Dev 21(24):3232–3237CrossRefPubMedPubMedCentral

30.

Topisirovic I, Ruiz-Gutierrez M, Borden KL (2004) Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes to its transformation and mRNAtransport activities. Cancer Res 64(23):8639–8642CrossRefPubMed

31.

Ho VK, Reijneveld JC, Enting RH, Bienfait HP, Robe P, Baumert BG, Visser O (2014) Dutch society for neuro-oncology (LWNO): changing incidence and improved survival of gliomas. Eur J Cancer 50(13):2309–2318CrossRefPubMed

32.

Pignatti F, van den Bent M, Curran D, Debruyne C, Sylvester R, Therasse P et al (2002) Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 20(8):2076–2084CrossRefPubMed

33.

Brandner S, von Deimling A (2015) Diagnostic, prognostic and predictive relevance of molecular markers in gliomas. Neuropathol Appl Neurobiol 41(6):694–720CrossRefPubMed

34.

Areeb Z, Stylli SS, Koldej R, Ritchie DS, Siegal T, Morokoff AP et al (2015) MicroRNA as potential biomarkers in Glioblastoma. J Neurooncol 125(2):237–248CrossRefPubMed

35.

Karsy M, Neil JA, Guan J, Mahan MA, Colman H, Jensen RL (2015) A practical review of prognostic correlations of molecular biomarkers in glioblastoma. Neurosurg Focus 38(3):E4CrossRefPubMed

Titel: Elevated levels of p-Mnk1, p-eIF4E and p-p70S6K proteins are associated with tumor recurrence and poor prognosis in astrocytomas
verfasst von: Weibing Fan
Weiyuan Wang
Xinfa Mao
Shuzhou Chu
Juan Feng
Desheng Xiao
Jianhua Zhou
Songqing Fan
Publikationsdatum: 29.11.2016
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2017
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-016-2327-2

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Vierten reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Bluttest erkennt Parkinson schon zehn Jahre vor der Diagnose

10.05.2024 Parkinson-Krankheit Nachrichten

Ein Bluttest kann abnorm aggregiertes Alpha-Synuclein bei einigen Menschen schon zehn Jahre vor Beginn der motorischen Parkinsonsymptome nachweisen. Mit einem solchen Test lassen sich möglicherweise Prodromalstadien erfassen und die Betroffenen früher behandeln.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2017

MCM7 expression is a promising predictor of recurrence in patients surgically resected for meningiomas

Impact of concurrent chemotherapy with radiation therapy for elderly patients with newly diagnosed glioblastoma: a review of the National Cancer Data Base

Erratum to: Epidemiology for primary brain tumors: a nationwide population-based study

Reverse phase protein arrays enable glioblastoma molecular subtyping

Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma