title: 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.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, Republic of South Africa.
authors.forename: Kerrilyn
authors.initials: K
authors.lastname: Naidoo
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, Republic of South Africa.
authors.forename: Sibusiso T
authors.initials: ST
authors.lastname: Malindisa
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, Republic of South Africa.
authors.forename: Tyrone C
authors.initials: TC
authors.lastname: Otgaar
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, Republic of South Africa.
authors.forename: Martin
authors.initials: M
authors.lastname: Bernert
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, Republic of South Africa.
authors.forename: Bianca
authors.initials: B
authors.lastname: Da Costa Dias
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, Republic of South Africa.
authors.forename: Eloise
authors.initials: E
authors.lastname: Ferreira
authors.affiliation: Affimed GmbH, Technologiepark, Im Neuenheimer Feld 582, 69120, Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Reusch
authors.affiliation: Affimed GmbH, Technologiepark, Im Neuenheimer Feld 582, 69120, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knackmuss
authors.affiliation: Affimed GmbH, Technologiepark, Im Neuenheimer Feld 582, 69120, Heidelberg, Germany.
authors.forename: Melvyn
authors.initials: M
authors.lastname: Little
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, Republic of South Africa.
authors.forename: Stefan F T
authors.initials: SF
authors.lastname: Weiss
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, Republic of South Africa.
authors.forename: Boitelo T
authors.initials: BT
authors.lastname: Letsolo
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D017474:Receptors, Laminin / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D012269:Ribosomal Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; D019098:Telomerase