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

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.

Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer

“…In our study, we found that NSCLC patients had high positive expression of p-mTOR and p-eIF4E proteins, which supports our previous findings in NPC and astrocytomas [38][39][40]. Expression of p-Akt was mainly localized in cytoplasm, a few in the nuclear or membrane, which indicates that p-Akt may play an important role in the cytoplasm and nucleus/ Overexpression of p-Akt, p-mTOR and p-eIF4E proteins in NSCLC membrane, thereby activating its downstream signaling pathway and promoting the development of tumors.…”

Dual Abrogation of Mnk and Mtor: A Novel Therapeutic Approach for the Treatment of Aggressive Cancers

“…Both MNK1 and MNK2 mRNAs have been found ubiquitously expressed in a variety of tissues by northern blot analysis. Fan et al recently observed a considerably higher percentage of active phospho-MNK in astrocytomas, further endorsing the role of active MNK in cancer [47,52]. High levels of phosphorylated MNK1 are also observed in HER-2 positive breast cancer and in glioblastoma multiforme primary tumors.…”

Beyond molecular tumor heterogeneity: protein synthesis takes control

“…3 and 4) [22]. Other groups have confirmed the prognostic importance of these factors in additional tumor types (Table 1), including colon cancer [61,62], nasopharyngeal carcinoma [63], hepatocellular carcinoma [64], astrocytomas [65], lung cancer [66,67], and melanoma [68]. Importantly, eIF4E is a central regulator of metastatic progression [69][70][71] (Fig.…”