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

PLoS One. 2015 Nov 6;10(11):e0141618. doi: 10.1371/journal.pone.0141618. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Grants and funding

This work was supported by the National Research Foundation, the Republic of South Africa. Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors, and therefore, the National Research Foundation does not accept any liability in this regard thereto. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The research from which this publication emanated was co-funded by the South African Medical Research Council (SAMRC). The specific roles of these authors are articulated in the "author contributions" section.