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

Kerrilyn Naidoo,Martin Bernert,Boitelo T Letsolo,Uwe Reusch,Melvyn Little,Bianca Da Costa Dias,Tyrone C Otgaar,Stefan F T Weiss,Sibusiso T Malindisa,Eloise Ferreira,Stefan Knackmuss

doi:10.1371/journal.pone.0141618

Kerrilyn Naidoo, Martin Bernert + Show 9 more

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https://doi.org/10.1371/journal.pone.0141618

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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.

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Cancer has become a major problem worldwide due to its increasing incidence and mortality rates
Since the overexpression of laminin receptor precursor/ high affinity laminin receptor (LRP/LR) and hTERT has been observed in numerous cancer cell lines, the levels of laminin receptor precursor (LRP)/LR and hTERT on the cell surface and intracellularly on HEK293 and MDA_MB231 cells were examined by flow cytometry
Flow cytometry revealed that 75.26% and 98.56% of HEK293 cells expressed LRP/LR and hTERT on the cell surface, respectively

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Cancer has become a major problem worldwide due to its increasing incidence and mortality rates. The t-loop is stabilised by the “Shelterin” complex [19] In this conformation, chromosome ends are protected from degradation and illegitimate processing which could results in premature senescence, recombination and end-to-end fusions and genome instability; a hallmark of cancer [20,21,22]. Telomerase is a holoenzyme and a cellular ribonucleoprotein that is involved in the addition of TTAGGG repeats to the 30end of chromosomes. It is composed of two essential components, the enzymatic reverse transcriptase catalytic subunit, hTERT and the integral RNA component, hTR or hTERC [30, 31]. As LRP/LR and hTERT both play a role in cancer progression and share sub-cellular localizations, we sought to investigate a possible correlation between LRP/LR and telomerase activity

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