Abstract
BackgroundThe 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in several tumourigenic-promoting processes including cellular viability maintenance and apoptotic evasion. Thus, the aim of this study was to assess the molecular mechanism of LRP/LR on apoptotic pathways in late stage (DLD-1) colorectal cancer cells upon siRNA-mediated down-regulation of LRP/LR.MethodssiRNAs were used to down-regulate the expression of LRP/LR in DLD-1 cells which was assessed using western blotting and qPCR. To evaluate the mechanistic role of LRP/LR, proteomic analysis of pathways involved in proliferation and apoptosis were investigated. The data from the study was analysed using a one-way ANOVA, followed by a two-tailed student’s t-test with a confidence interval of 95%.ResultsHere we show that knock-down of LRP/LR led to significant changes in the proteome of DLD-1 cells, exposing new roles of the protein. Moreover, analysis showed that LRP/LR may alter components of the MAPK, p53-apoptotic and autophagic signalling pathways to aid colorectal cancer cells in continuous growth and survival. Knock-down of LRP/LR also resulted in significant decreases in telomerase activity and telomerase-related proteins in the DLD-1 cells.ConclusionsThese findings show that LRP/LR is critically implicated in apoptosis and cell viability maintenance and suggest that siRNA-mediated knock-down of LRP/LR may be a possible therapeutic strategy for the treatment of colorectal cancer.
Highlights
The 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in several tumourigenic-promoting processes including cellular viability maintenance and apoptotic evasion
Due to LRP/ LR’s role in cell viability maintenance, cell cycle analysis was performed in order to obtain insight into the effect of Laminin receptor precursor/high-affinity laminin receptor (LRP/LR) knock-down as well as to confirm the occurrence of apoptosis
We have previously shown that the knock-down of LRP/LR via Small interfering RNA (siRNA) technology significantly reduced the viability of early (SW-480) and late (DLD-1) stage colorectal cancer cells through the induction of apoptosis [18]
Summary
The 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in several tumourigenic-promoting processes including cellular viability maintenance and apoptotic evasion. Research into the 37 kDa/ 67 kDa laminin receptor (LRP/LR) has gained a large amount of interest as it plays several physiological roles within cells [2]. These include ribosomal processing and protein translation [3], nuclear structure maintenance [4, 5], and linking of ribosomes to microtubules [6]. In addition to these physiological roles, LRP/LR is found to have pathological roles in several diseases [7,8,9,10].
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