Knock-Down of the 37kDa/67kDa Laminin Receptor LRP/LR Impedes Telomerase Activity

• Published in: PloS one 2015-11, Vol.10 (11), p.e0141618-e0141618
• Main Authors: Naidoo, Kerrilyn, Malindisa, Sibusiso T, Otgaar, Tyrone C, Bernert, Martin, Da Costa Dias, Bianca, Ferreira, Eloise, Reusch, Uwe, Knackmuss, Stefan, Little, Melvyn, Weiss, Stefan F T, Letsolo, Boitelo T
• Format: Article
• Language: English
• Subjects: Aging; Angiogenesis; Apoptosis; Breast cancer; Cancer; Cancer therapies; Cell differentiation; Cell Nucleus - metabolism; Cell surface; Chromosomes; Cytometry; Deoxyribonucleic acid; DNA; Flow cytometry; Gene Expression Regulation - genetics; Gene Knockdown Techniques; Genetic aspects; Health aspects; HEK293 Cells; Humans; Immunoprecipitation; Invasiveness; Laminin; Metastases; Molecular biology; Protein Transport - genetics; Receptors, Laminin - deficiency; Receptors, Laminin - genetics; Receptors, Laminin - metabolism; Ribosomal Proteins - deficiency; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; RNA, Small Interfering - genetics; RNA-mediated interference; Senescence; siRNA; Telomerase; Telomerase - metabolism; Telomerase reverse transcriptase
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141618

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.