Interactions between PrPc and other ligands with the 37-kDa/67-kDa laminin receptor

Mbazima,; B, Da Costa Dias; Omar, Aadilah; Jovanović, Katarina; Sf, Weiss

doi:10.2741/3667

Cited by 35 publications

(9 citation statements)

References 91 publications

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“…the cell surface, nucleus, perinuclear compartment and cytosol thus mediating crucial physiological processes. However the high levels of LRP expression in cancer cells allow these cells to override these processes for survival purposes[ 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…The pathological potential of LRP/LR in cancer has been targeted using numerous anti-LRP/LR tools including anti-LRP/LR specific antibodies in order to impede cancer propagating processes including, increased invasion[ 3 ], cellular proliferation[ 44 ], metastasis[ 29 , 33 ] and evasion of apoptosis[ 36 ]. Therefore, targeting of LRP/LR poses as a promising alternative therapeutic approach for the treatment of cancer by hampering the occurrence of the above mentioned cancer promoting processes.…”

Section: Discussionmentioning

confidence: 99%

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Knockdown of LRP/LR Induces Apoptosis in Breast and Oesophageal Cancer Cells

et al. 2015

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Cancer is a global burden due to high incidence and mortality rates and is ranked the second most diagnosed disease amongst non-communicable diseases in South Africa. A high expression level of the 37kDa/67kDa laminin receptor (LRP/LR) is one characteristic of cancer cells. This receptor is implicated in the pathogenesis of cancer cells by supporting tumor angiogenesis, metastasis and especially for this study, the evasion of apoptosis. In the current study, the role of LRP/LR on cellular viability of breast MCF-7, MDA-MB 231 and WHCO1 oesophageal cancer cells was investigated. Western blot analysis revealed that total LRP expression levels of MCF-7, MDA-MB 231 and WHCO1 were significantly downregulated by targeting LRP mRNA using siRNA-LAMR1. This knockdown of LRP/LR resulted in a significant decrease of viability in the breast and oesophageal cancer cells as determined by an MTT assay. Transfection of MDA-MB 231 cells with esiRNA-RPSA directed against a different region of the LRP mRNA had similar effects on LRP/LR expression and cell viability compared to siRNA-LAMR1, excluding an off-target effect of siRNA-LAMR1. This reduction in cellular viability is as a consequence of apoptosis induction as indicated by the exposure of the phosphatidylserine protein on the surface of breast MCF-7, MDA-MB 231 and oesophageal WHCO1 cancer cells, respectively, detected by an Annexin-V/FITC assay as well as nuclear morphological changes observed post-staining with Hoechst. These observations indicate that LRP/LR is crucial for the maintenance of cellular viability of breast and oesophageal cancer cells and recommend siRNA technology targeting LRP expression as a possible novel alternative technique for breast and oesophageal cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Knockdown of LRP/LR Induces Apoptosis in Breast and Oesophageal Cancer Cells

et al. 2015

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“…22 LRP/LR is involved in various tumorigenic processes, and the upregulation of PrP C and LRP/LR in gastric tumors predicts poor prognosis. 22 LRP/LR is involved in various tumorigenic processes, and the upregulation of PrP C and LRP/LR in gastric tumors predicts poor prognosis.…”

Section: Prp C Engagement To Its Ligands: a Reliable Target For Theramentioning

confidence: 99%

Targeting prion protein interactions in cancer

Santos

Lopes

Martins

2015

Prion

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In recent years, prion protein (PrP(C)) has been considered as a promising target molecule for cancer therapies, due its direct or indirect participation in tumor growth, metastasis, and resistance to cell death induced by chemotherapy. PrP(C) functions as a scaffold protein, forming multiprotein complexes on the plasma membrane, which elicits distinct signaling pathways involved in diverse biological phenomena and could be modulated depending on the cell type, complex composition, and organization. In addition, PrP(C) and its partners participate in self-renewal of embryonic, tissue-specific stem cells and cancer stem cells, which are suggested to be responsible for the origin, maintenance, relapse, and dissemination of tumors. Interference with protein-protein interaction has been recognized as an important therapeutic strategy in cancer; indeed, the possible interference in PrP(C) engagement with specific partners is a novel strategy. Recently, our group successfully used that approach to interfere with the interaction between PrP(C) and HSP-90/70 organizing protein (HOP, also known as stress-inducible protein 1 - STI1) to control the growth of human glioblastoma in animal models. Thus, PrP(C)-organized multicomplexes have emerged as feasible candidates for anti-tumor therapy, warranting further exploration.

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“…The proposed mechanism by which Aβ is generated involves the sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by β-secretase and the γ-secretase complex. [2][3][4] Sangram Sisodia (University of Chicago) opened the conference with an elucidating overview on the function of presenilin (PS), the catalytic subunit of the γ-secretase complex, in health and disease. He presented findings aimed at describing the γ-secretase complex and its function, as well as the importance of PS in autophagy.…”

Section: Molecular Mechanismsmentioning

confidence: 99%