Cellular prion protein transcriptionally regulated by NFIL3 enhances lung cancer cell lamellipodium formation and migration through JNK signaling

Lin, Shin; Lin, Chia Hung; Shih, N.; Liu, Hsin Ling; Wang, Wen Chao; Lin, Kun; Liu, Zih Yu; Tseng, Yu Jhen; Chang, Hsueh Kai; Lin, Yi; Yeh, Yi Chen; Minato, Hiroshi; Fujii, Takeshi; Wu, Yu Chung; Chen, Mei Yu; Chou, Teh Ying

doi:10.1038/s41388-019-0994-0

Cited by 33 publications

(33 citation statements)

References 50 publications

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“…Cell motility mechanisms are quite relevant for cancer survival and are orchestrated by a variety of molecules, including prion protein. The processes of invasion and metastasis allow cancer cells to spread throughout tissues [ 89 ], which hinders surgical resections and therapy [ 90 , 91 , 92 ]. These malignant behaviors are associated with poor prognoses and higher recurrence rates of several cancer types, such as colorectal adenocarcinoma [ 93 ], glioblastoma [ 94 ], metastatic gastric cancer [ 95 ], and melanoma [ 96 ].…”

Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

“…Regarding lung cancer, the PRNP gene is upregulated by NFIL3 in invasive lung adenocarcinoma (ILA) cell lines [ 90 ] and, at the protein level, PrP C expression is widely observed in invasive tumors, but not in in situ tumors [ 90 ]. Furthermore, lamellipodia regions of ILA cell lines show augmented PrP C expression, and this protein modulates the levels of active Rac1 and the migration of these cells [ 90 ]. PrP C has been implicated in the metastatic capability of ILA in in vivo assays, and PrP C interaction with the JNK pathway induces the motility of ILA cell lines [ 90 ].…”

Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

“…Furthermore, lamellipodia regions of ILA cell lines show augmented PrP C expression, and this protein modulates the levels of active Rac1 and the migration of these cells [ 90 ]. PrP C has been implicated in the metastatic capability of ILA in in vivo assays, and PrP C interaction with the JNK pathway induces the motility of ILA cell lines [ 90 ]. In addition, NFIL3 and PrP C act towards cancer cell migration [ 90 ].…”

Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

“…PrP C has been implicated in the metastatic capability of ILA in in vivo assays, and PrP C interaction with the JNK pathway induces the motility of ILA cell lines [ 90 ]. In addition, NFIL3 and PrP C act towards cancer cell migration [ 90 ].…”

Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

“…Interestingly, whereas some non-neoplastic tissues present low PrP C expression, this protein is upregulated in cancer tissue samples [ 116 , 119 ]. Moreover, PrP C also shows higher expression in invasive and metastatic cancers compared with non-invasive and non-metastatic ones [ 90 , 123 ].…”

Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

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Prion Protein at the Leading Edge: Its Role in Cell Motility

Prado

Escobar

Alves

et al. 2020

IJMS

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Cell motility is a central process involved in fundamental biological phenomena during embryonic development, wound healing, immune surveillance, and cancer spreading. Cell movement is complex and dynamic and requires the coordinated activity of cytoskeletal, membrane, adhesion and extracellular proteins. Cellular prion protein (PrPC) has been implicated in distinct aspects of cell motility, including axonal growth, transendothelial migration, epithelial–mesenchymal transition, formation of lamellipodia, and tumor migration and invasion. The preferential location of PrPC on cell membrane favors its function as a pivotal molecule in cell motile phenotype, being able to serve as a scaffold protein for extracellular matrix proteins, cell surface receptors, and cytoskeletal multiprotein complexes to modulate their activities in cellular movement. Evidence points to PrPC mediating interactions of multiple key elements of cell motility at the intra- and extracellular levels, such as integrins and matrix proteins, also regulating cell adhesion molecule stability and cell adhesion cytoskeleton dynamics. Understanding the molecular mechanisms that govern cell motility is critical for tissue homeostasis, since uncontrolled cell movement results in pathological conditions such as developmental diseases and tumor dissemination. In this review, we discuss the relevant contribution of PrPC in several aspects of cell motility, unveiling new insights into both PrPC function and mechanism in a multifaceted manner either in physiological or pathological contexts.

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Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

Section: Cellular Prion Protein In Cancer Cell Motilitymentioning

confidence: 99%

See 3 more Smart Citations

Prion Protein at the Leading Edge: Its Role in Cell Motility

Prado

Escobar

Alves

et al. 2020

IJMS

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Role of hemoglobin alpha and hemoglobin beta in non‐small‐cell lung cancer based on bioinformatics analysis

Kang

Qiu

Wang

et al. 2022

Molecular Carcinogenesis

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The differentially expressed genes (DEGs) were identified and screened differentially in non‐small‐cell lung cancer (NSCLC) using information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases, and the correlation of DEGs in protein interaction, function, and pathway enrichment were analyzed to search for new biomarkers and potential therapeutic targets for NSCLC. Protein–protein interaction network (PPI) analysis showed that CDK1 and GNGT1 were the most significantly upregulated hub nodes, while FPR2 was the most significantly downregulated. Gene Ontology enrichment analysis showed that upregulated DEGs were significantly enriched in protein heterodimerization activity and other functions, while downregulated DEGs were enriched in functions such as heparin‐binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that upregulation of DEGs were significantly associated with neuroactive ligand‐receptor interaction pathways, while downregulation of DEGs were significantly associated with malaria pathways. According to the analysis results, we identified hemoglobin alpha (HBA) and hemoglobin beta (HBB) as the genes of interest for further study. Through tissue level and cell level experiments, we found that the expressions of HBA and HBB in NSCLC tissues were significantly lower than those in paracancerous tissues, and downregulation of HBA and HBB could significantly affect the proliferation ability of NSCLC cells. In addition, we also found that changes in HBA and HBB may affect NSCLC cells through the p38/MAPK pathway and JNK pathway, and ultimately affect the occurrence and development of NSCLC.

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Emerging roles of the cellular prion protein (PrPC) and 37/67 kDa laminin receptor (RPSA) interaction in cancer biology

Limone

Maggisano

Sarnataro

et al. 2023

Cell. Mol. Life Sci.

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The cellular prion protein (PrPC) is well-known for its involvement, under its pathogenic protease-resistant form (PrPSc), in a group of neurodegenerative diseases, known as prion diseases. PrPC is expressed in nervous system, as well as in other peripheral organs, and has been found overexpressed in several types of solid tumors. Notwithstanding, studies in recent years have disclosed an emerging role for PrPC in various cancer associated processes. PrPC has high binding affinity for 37/67 kDa laminin receptor (RPSA), a molecule that acts as a key player in tumorigenesis, affecting cell growth, adhesion, migration, invasion and cell death processes. Recently, we have characterized at cellular level, small molecules able to antagonize the direct PrPC binding to RPSA and their intracellular trafficking. These findings are very crucial considering that the main function of RPSA is to modulate key events in the metastasis cascade. Elucidation of the role played by PrPC/RPSA interaction in regulating tumor development, progression and response to treatment, represents a very promising challenge to gain pathogenetic information and discover novel specific biomarkers and/or therapeutic targets to be exploited in clinical settings. This review attempts to convey a detailed description of the complexity surrounding these multifaceted proteins from the perspective of cancer hallmarks, but with a specific focus on the role of their interaction in the control of proliferation, migration and invasion, genome instability and mutation, as well as resistance to cell death controlled by autophagic pathway.

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Cellular prion protein transcriptionally regulated by NFIL3 enhances lung cancer cell lamellipodium formation and migration through JNK signaling

Cited by 33 publications

References 50 publications

Prion Protein at the Leading Edge: Its Role in Cell Motility

Prion Protein at the Leading Edge: Its Role in Cell Motility

Role of hemoglobin alpha and hemoglobin beta in non‐small‐cell lung cancer based on bioinformatics analysis

Emerging roles of the cellular prion protein (PrPC) and 37/67 kDa laminin receptor (RPSA) interaction in cancer biology

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