Knock-down of the 37kDa/67kDa laminin receptor LRP/LR impedes telomerase activity.

Date
2015-11-06
Authors
Naidoo, K.
Malindisa, S.T.
Otgaar, T.C.
Da Costa Dias, B.
Ferreirra, E.
Reusch, U.
Knackmuss, S.
Little, M.
Weiss, S.F.T.
Letsolo, B.T.
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science.
Abstract
Cancer has become a major problem worldwide due to its increasing incidence and mortality rates. Both the 37kDa/67kDa laminin receptor (LRP/LR) and telomerase are overexpressed in cancer cells. LRP/LR enhances the invasiveness of cancer cells thereby promoting metastasis, supporting angiogenesis and hampering apoptosis. An essential component of telomerase, hTERT is overexpressed in 85-90% of most cancers. hTERT expression and increased telomerase activity are associated with tumor progression. As LRP/LR and hTERT both play a role in cancer progression, we investigated a possible correlation between LRP/LR and telomerase. LRP/LR and hTERT co-localized in the perinuclear compartment of tumorigenic breast cancer (MDA-MB231) cells and non-tumorigenic human embryonic kidney (HEK293) cells. FLAG® Co-immunoprecipitation assays confirmed an interaction between LRP/LR and hTERT. In addition, flow cytometry revealed that both cell lines displayed high cell surface and intracellular LRP/LR and hTERT levels. Knock-down of LRP/LR by RNAi technology significantly reduced telomerase activity. These results suggest for the first time a novel function of LRP/LR in contributing to telomerase activity. siRNAs targeting LRP/LR may act as a potential alternative therapeutic tool for cancer treatment by (i) blocking metastasis (ii) promoting angiogenesis (iii) inducing apoptosis and (iv) impeding telomerase activity.
Description
Keywords
laminin receptor;, small interfering RNA;, telomerase;, breast cancer;, cancer cell line;, cell level;, cell nucleus;, cell surface;, controlled study;, embryo;, enzyme activity;, gene silencing;, HEK293 cell line;, human; human cell;, MB231 cell line;, protein function;, protein localization;, protein protein interaction;, RNA interference;
Citation
Naidoo, K. et al. 2015. Knock-down of the 37kDa/67kDa laminin receptor LRP/LR impedes telomerase activity. PLoS ONE 10(11): e0141618.