The more basic isoform of eEF1A relates to tumour cell phenotype and is modulated by hyper‐proliferative/differentiating stimuli in normal lymphocytes and CCRF‐CEM T‐lymphoblasts

Abstract

The elongation factor 1A proteins (eEF1A1/A2) are known to play a role in tumours. We previously found that a more basic isoform of eEF1A (MBI-eEF1A) is present in the cytoskeletal/nuclear-enriched extracts of CCRF-CEM T-lymphoblasts but not in those of normal lymphocytes. To obtain deeper knowledge about MBI-eEF1A biology, we investigate from which of the eEF1A proteins, eEF1A1 or eEF1A2, MBI-eEF1A originates and the possibility that its appearance can be modulated by the differentiated or proliferative cell status. CCRF-CEM T-lymphoblasts and normal lymphocytes were cultured with or without differentiation/pro-proliferative stimuli (Phorbol 12-Myristate 13-Acetate (PMA) alone or the combination of phytohaemagglutinin (PHA) with PMA, respectively), and the presence of MBI-eEF1A evaluated together with that of the eEF1A1/A2 mRNAs. Our data indicate that the MBI-eEF1A may derive from eEF1A1 as eEF1A2 is not expressed in CCRF-CEM and normal lymphocytes. Moreover, MBI-eEF1A is inducible in normal lymphocytes upon hyper-proliferative stimuli application; in CCRF-CEM, its presence can be abrogated by PMA-induced differentiation. Finally, MBI-eEF1A may have a functional role in hyper-proliferating/tumour cells as its disappearance reduces the growth of CCRF-CEM and that of PHA/PMA-stimulated lymphocytes. The presented data suggest that MBI-eEF1A may be related to oncogenic cell phenotype, rising the possibility to use MBI-eEF1A as target for novel therapeutic strategies.

Aptamer targeting of the elongation factor 1A impairs hepatocarcinoma cells viability and potentiates bortezomib and idarubicin effects

“…GT75 derives from a shorter aptamer version (GT27) shown to be effective in reducing the viability of a variety of leukemic cells (Dapas et al, 2003a;Morassutti et al, 1999;Scaggiante et al, 2006aScaggiante et al, , 2013bScaggiante et al, , 1998. Here we provide evidences (Fig.…”

“…In this work, we explore the effects of eEF1A targeting by a single stranded DNA aptamer containing GT repetitions in HCC cell lines. We have previously demonstrated that GT aptamers containing either 27 (GT27) or 51 GT (GT51) repetitions can specifically bind to the eEF1A protein derived from the nuclear/ cytoskeletal-enriched compartment of a variety of leukemic cells (Dapas et al, 2003a;Morassutti et al, 1999;Scaggiante et al, 2006aScaggiante et al, , 2013bScaggiante et al, , 1998. Notably, eEF1A targeting resulted in a remarkable impairment of cell vitality showing a potent antitumor effect in leukemic cells.…”

EEF1A1 (eukaryotic translation elongation factor 1 alpha 1)

“…Moreover the more basic isoform expression can be induced by phorbol ester in normal human lymphocytes and inhibited in T-lymphoblastic CCRF-CEM cancer cell line upon differentiation stimuli. Thus, this suggests a role of the more basic isoform in leukemia onset (Scaggiante et al, 2013). In human acute T lymphocytic leukemia Jurkat cell line, eEF1A1 expression sustained cell proliferation inhibiting apoptosis by up-regulating PI3K/Akt/NFkB and PI3K/Akt/mTOR signaling pathway (Huang et al, 2013).…”

Epigenetic and miRNAs Dysregulation in Prostate Cancer: The role of Nutraceuticals

“…Beyond their role in translation, eEF1A1 and eEF1A2 are involved in the regulation of several physiological processes by their non-canonical functions, which include actin binding and modulation of cytoskeleton, cell death and participation in signalling pathways, including cytokine and TGF-beta signalling [ 23 - 26 ]. The eEF1A1 expression has been found to be de- regulated in some tumors [ 21 , 22 , 24 , 26 ], while the activation of eEF1A2 expression is recognized to play a role in tumorigenesis and progression of many cancers [ 20 ]. The over-expression of eEF1A proteins has been recently found in PCa cells, and the eEF1A2 expression has been suggested to mark prostate tumor onset and progression [ 20 ].…”