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

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.

• Authors: Kerrilyn Naidoo, Sibusiso T Malindisa, Tyrone C Otgaar, Martin Bernert, Bianca Da Costa Dias, Eloise Ferreira, Uwe Reusch, Stefan Knackmuss, Melvyn Little, Stefan F T Weiss, Boitelo T Letsolo
• Journal: PloS one (PLoS One) Vol. 10 Issue 11 Pg. e0141618 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26545108 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• RPSA protein, human
• Receptors, Laminin
• Ribosomal Proteins
• Telomerase

Topics

• Cell Nucleus (metabolism)
• Gene Expression Regulation (genetics)
• Gene Knockdown Techniques
• HEK293 Cells
• Humans
• Protein Transport (genetics)
• RNA, Small Interfering (genetics)
• Receptors, Laminin (deficiency, genetics, metabolism)
• Ribosomal Proteins (deficiency, genetics, metabolism)
• Telomerase (metabolism)