Retinoic acid-mediated down-regulation of ENO1/MBP-1 gene products caused decreased invasiveness of the follicular thyroid carcinoma cell lines

Abstract

Retinoic acid (RA) acts as an anti-proliferative and redifferentiation agent in the therapy of thyroid carcinoma. Our previous studies demonstrated that pretreatment of follicular thyroid carcinoma cell lines FTC-133 and FTC-238 resulted in decreased in vitro proliferation rates and reduced tumor cell growth of xenotransplants. In addition to the previous results, we found that RA led to decreased vitality and invasiveness of FTC-133 and FTC-238 cells as they reacted with reduction of intracellular ATP levels and number of migrated cells respectively. However, the molecular mechanisms by which RA mediates these effects are not well understood. Two-dimensional (2D) screening of the proteins related to ATP metabolism and western blot analysis revealed a-enolase (ENO1) to be down-regulated in FTC-133 and FTC-238 cells after RA treatment. 2D gel detection and mass spectrometric analysis revealed that ENO1 existed as three separate protein spots of distinct pIs (ENO1-A1-A3). Comparative 2D difference gel electrophoresis analysis of fluorescently labeled protein samples of RA-treated and untreated FTC-133 demonstrated a selective down-regulation of ENO1-A1 which we identified as a phosphoprotein. RA caused the dephosphorylation of ENO1-A1. Both, RA-mediated and specific knock-down of ENO1/MBP-1 resulted in the reduction of MYC oncoprotein, and simultaneously decreased proliferation rates of FTC-133 and FTC-238 cell lines. In summary, the RA-mediated down-regulation of the ENO1 gene products and MYC oncoprotein provides a novel molecular mechanism facilitating the anti-proliferative effect of RA in human thyroid carcinoma cells and suggests new pathways for supportive RA therapies.

Alpha-enolase (ENO1) controls alpha v/beta 3 integrin expression and regulates pancreatic cancer adhesion, invasion, and metastasis

“…These data correlate well with previous observations in follicular thyroid carcinoma [38], glioma [13], non-small cell lung cancer [14], and endometrial cancer [15], again supporting the emerging role of ENO1 as a promising target for cancer treatment. However, although blocking surface ENO1 impaired the ability of PDA cells to migrate in vitro and form more metastasis in vivo [12], little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts.…”

Antioxidant-rich leaf extract ofBarringtonia racemosasignificantly alters thein vitroexpression of genes encoding enzymes that are involved in methylglyoxal degradation III

“…In gluconeogenesis, this enzyme catalyzes the hydration of phosphoenolpyruvate (PEP) to phospho-D-glycerate (PGA) (Trojanowicz et al, 2009). Thus, down-regulation of ENO3 gene expression and subsequently the encoded protein may prevent the growth of cancer cells.…”

α-Enolase, a Multifunctional Protein: Its Role on Pathophysiological Situations

“…Knockdown of α -enolase expression in different tumor cell lines caused a dramatic increase in their sensitivity to microtubule targeted drugs (e.g., taxanes and vincristine), probably due to α -enolase-tubulin interactions [103], suggesting a role for α -enolase in modulating the microtubule network. Downregulation of α -enolase gene product deceased invasiveness of the follicular thyroid carcinoma cell lines [104]. α -Enolase overexpression has been associated with head and neck cancer cells, and this increase associated not only with cancer progression but also with poor clinical outcomes.…”