1. Knock-Down of the 37kDa/67kDa Laminin Receptor LRP/LR Impedes Telomerase Activity.
- Author
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Naidoo K, Malindisa ST, Otgaar TC, Bernert M, Da Costa Dias B, Ferreira E, Reusch U, Knackmuss S, Little M, Weiss SF, and Letsolo BT
- Subjects
- Cell Nucleus metabolism, Gene Expression Regulation genetics, HEK293 Cells, Humans, Protein Transport genetics, RNA, Small Interfering genetics, Receptors, Laminin metabolism, Ribosomal Proteins metabolism, Gene Knockdown Techniques, Receptors, Laminin deficiency, Receptors, Laminin genetics, Ribosomal Proteins deficiency, Ribosomal Proteins genetics, Telomerase metabolism
- 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.
- Published
- 2015
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