Patented therapeutic approaches targeting LRP/LR for cancer treatment

Vania, Leila; Morris, Gavin; Otgaar, Tyrone C; Bignoux, Monique J; Bernert, Martin; Burns, Jessica; Gabathuse, Anne; Singh, Elvira; Ferreira, Eloise; Weiß, Stefan

doi:10.1080/13543776.2019.1693543

Cited by 19 publications

(18 citation statements)

References 156 publications

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“…19 Interactions between the non-integrin LR and laminin play a key role in mediating changes in ECM that affect cell adhesion, neurite outgrowth, angiogenesis, and apoptosis. 20,21 The non-integrin LR is required for maintenance of cell viability by preventing apoptosis. 22,23 Previous study demonstrated that siRNA-mediated knockdown of non-integrin LR reduced FAK phosphorylation, leading to cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

Zhang

Sun

et al. 2020

CNS Neurosci Ther

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Aims During early development, laminin degradation contributes to the death of neurons. This study aims to investigate the role and regulation of laminin in ketamine‐induced apoptosis. Methods We performed terminal deoxynucleotidyl transferase biotin‐dUTP nick end labeling (TUNEL) and immunohistochemical assays to investigate the roles of the non‐integrin laminin receptor, matrix metalloproteinase 9 (MMP9) in ketamine‐induced neuronal apoptosis. In situ zymography, Western blot, and immunofluorescence were used to explore the relationships between laminin, MMP9 activity, and Zn2+. Experiments were performed using whole‐mount retinas dissected from Sprague Dawley rats. Results The TUNEL and immunohistochemical assays indicated that ketamine‐induced neuronal apoptosis in early developing rat retina. Blockade of non‐integrin laminin receptor promoted ketamine‐induced apoptosis, while non‐integrin laminin receptor activation attenuated ketamine‐induced apoptosis. Ketamine‐induced laminin degradation, possibly by enhancing the activity of MMP9. MMP9 inhibition reduced ketamine‐induced apoptosis by reducing laminin degradation. Downregulation of Zn2+ attenuated the increased MMP9 activity, laminin degradation caused by ketamine and significantly reduced ketamine‐induced neuronal apoptosis. Conclusion Laminin degradation by MMP9 promoted ketamine‐induced neuronal apoptosis in early developing rat retina. The non‐integrin laminin receptor may be a pathway involved in ketamine‐induced apoptosis. Zn2+ downregulation may play a protective role against ketamine‐induced neuronal apoptosis through inhibiting MMP9 activity.

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Section: Introductionmentioning

confidence: 99%

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

Zhang

Sun

et al. 2020

CNS Neurosci Ther

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“…Recent data suggest that LAMR interaction with FAK may depend on laminin 1—LAMR interaction and promote Ras/MAPK and/or PI3K/AKT-mediated survival ( 297 , 298 ). However, LAMR was found to promote tumor progression through various laminin 1-independent manners, such as regulation of telomerases ( 299 ), reviewed in ( 300 ).…”

Section: Non-integrin Tumor Cell Receptors To the Ecmmentioning

confidence: 99%

“…Despite various emerging strategies aimed to target LAMR ( 300 ), in vivo preclinical studies assessing the feasibility and efficiency of targeting LAMR are still scant. Both a LAMR 37 blocking antibody and a small molecule inhibitor preventing laminin-LAMR interaction were shown to impede metastatic progression ( Table 1 ).…”

Section: Non-integrin Tumor Cell Receptors To the Ecmmentioning

confidence: 99%

Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors

2020

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“…It was reported to enhance tumor cell invasion and adhesion as well as angiogenesis, key steps in tumor progression. Recent findings have shown that RPSA is involved in the maintenance of cell viability through apoptotic evasion, allowing tumor progression ( Vania et al, 2019 ). The green-tea-derived polyphenol, (−)-epigallocatechin-3-gallate (EGCG), is a small molecule that was reported to affect cell behavior through RPSA binding and cytoskeletal alterations.…”

Section: Introductionmentioning

confidence: 99%

TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration

Lefebvre

Rybarczyk

Bretaudeau

et al. 2020

Front. Cell Dev. Biol.

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Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a very poor prognosis due to highly metastatic profile. Cell migration is an essential step of the metastatic cascade allowing cancer cells to spread toward target tissues. Recent studies strongly suggest that bioactive elastin peptides, also named elastokines or elastin-derived peptides (EDPs), are released in the extracellular microenvironment during tumoral remodeling of the stroma. EDPs stimulate cancer cell migration by interacting with their membrane receptor, ribosomal protein SA (RPSA). Others membrane proteins like ion channels are also involved in cancer cell migration. It has been recently shown that the transient receptor potential melastatin-related 7 (TRPM7) channel regulates PDAC cell migration and invasion. The objective of this work was to study the effect of EDPs on TRPM7 channel in human pancreatic cancer cells. We showed that EDPs promote MIA PaCa-2 cell migration using Boyden chamber assay. Cells transfected with a siRNA targeting TRPM7 were not able to migrate in response to EDPs indicating that TRPM7 regulated cell migration induced by these peptides. Moreover, EDPs were able to stimulate TRPM7 currents recorded by Patch-Clamp. Finally, we showed that TRPM7 channels and RPSA receptors are colocalized at the plasma membrane of human pancreatic cancer cells. Taken together, our data suggest that TRPM7/RPSA complex regulated human pancreatic cancer cell migration. This complex may be a promising therapeutic target in PDAC.

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Patented therapeutic approaches targeting LRP/LR for cancer treatment

Cited by 19 publications

References 156 publications

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors

TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration

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