Binding of pro-prion to filamin A disrupts cytoskeleton and correlates with poor prognosis in pancreatic cancer

Li, Chaoyang; Yu, Shuiliang; Nakamura, Fumihiko; Yin, Shaoman; Xu, Jinghua; Petrolla, Amber A.; Singh, Neena; Tartakoff, Alan M.; Abbott, Derek W.; Wei, Xin; Sy, Man Sun

doi:10.1172/jci39542

Cited by 91 publications

(139 citation statements)

References 67 publications

(44 reference statements)

Supporting

Mentioning

127

Contrasting

Order By: Relevance

“…We treated AsPC-1 and BxPC-3 cells with PI-PLC. PI-PLC treatment is a well established assay to determine whether a protein is GPI-anchored or not (11,41). Using mAb 4H2, we found that although the PrP on the cell surface of BxPC-3 was highly resistant to PI-PLC, the PrP on the surface of AsPC-1 was much more susceptible to identical treatment ( Fig.…”

Section: Prp From Aspc-1 But Not Bxpc-3 Is Sensitive To Pi-plc Treatmmentioning

confidence: 90%

“…Because carboxypeptidase digests amino acids from the C terminus of a protein, it will not be able to cleave GPI-anchored PrP (11). We treated the immunopurified PrP with carboxypeptidase Y and found the enzyme degraded PrP from BxPC-3 much more readily than PrP from AsPC-1 (Fig.…”

Section: Prp From Aspc-1 But Not Bxpc-3 Is Sensitive To Pi-plc Treatmmentioning

confidence: 99%

“…The up-regulation of PrP has been reported to contribute to tumor cell migration, proliferation, and multiple drug resistance (9,(15)(16)(17). More importantly, increased PrP expression is a biomarker for poor prognostics for patients with pancreatic cancer, breast cancer, or gastric cancer (11,13,18). Previously, in our studies of six PDAC cell lines and a melanoma cell line, we found that the PrP existed as a pro-PrP, as defined by retaining its normally cleaved GPI-PSS (11,12).…”

Section: Prpmentioning

confidence: 99%

“…More importantly, increased PrP expression is a biomarker for poor prognostics for patients with pancreatic cancer, breast cancer, or gastric cancer (11,13,18). Previously, in our studies of six PDAC cell lines and a melanoma cell line, we found that the PrP existed as a pro-PrP, as defined by retaining its normally cleaved GPI-PSS (11,12). Sequencing of the open reading frame (ORF) of PRNP in these cell lines did not identify any mutations.…”

Section: Prpmentioning

confidence: 99%

“…FLNa is a cytolinker protein that is important in linking cell surface receptors to the cytoskeleton (19,20). Hence, binding of pro-PrP to FLNa alters the normal physiology of FLNa rendering the tumor cell to be more aggressive (11,12).…”

Section: Prpmentioning

confidence: 99%

See 4 more Smart Citations

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility

Yang

Gao

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP.

show abstract

Section: Prp From Aspc-1 But Not Bxpc-3 Is Sensitive To Pi-plc Treatmmentioning

confidence: 90%

Section: Prp From Aspc-1 But Not Bxpc-3 Is Sensitive To Pi-plc Treatmmentioning

confidence: 99%

Section: Prpmentioning

confidence: 99%

Section: Prpmentioning

confidence: 99%

Section: Prpmentioning

confidence: 99%

See 3 more Smart Citations

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility

Yang

Gao

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

EGFR and Prion protein promote signaling via FOXO3a‐KLF5 resulting in clinical resistance to platinum agents in colorectal cancer

et al. 2019

View full text Add to dashboard Cite

Epidermal growth factor receptor ( EGFR ) supports colorectal cancer progression via oncogenic signaling. Anti‐ EGFR therapy is being investigated as a clinical option for colorectal cancer, and an observed interaction between EGFR and Prion protein has been detected in neuronal cells. We hypothesized that Pr P C expression levels may regulate EGFR signaling and that detailed understanding of this signaling pathway may enable identification of resistance mechanisms and new actionable targets in colorectal cancer. We performed molecular pathway analysis following knockdown of Pr P C or inhibition of EGFR signaling via gefitinib to identify changes in expression of key signaling proteins that determine cellular sensitivity or resistance to cisplatin. Expression of these proteins was examined in matched primary and metastatic patient samples and was correlated for resistance to therapy and progression of disease. Utilizing three colorectal cancer cell lines, we observed a correlation between high expression of Pr P C and resistance to cisplatin. Investigation of molecular signaling in a resistant cell line revealed that Pr P C contributed to signaling via colocalization with EGFR , which could be overcome by targeting p38 mitogen‐activated protein kinases (p38 MAPK ). We revealed that the level of Krüppel‐like factor 5 ( KLF 5), a target downstream of p38 MAPK , was predictive for cell line and patient response to platinum agents. Further, high KLF 5 expression was observed in BRAF ‐mutant colorectal cancer. Our study indicates that the EGFR to KLF 5 pathway is predictive of patient progression on platinum‐based therapy.

show abstract

Investigation of Glycosylphosphatidylinositol (GPI)‐Plasma Membrane Interaction in Live Cells and the Influence of GPI Glycan Structure on the Interaction

Kundu,

Jaiswal,

Babu Mullapudi

et al. 2023

Chemistry A European J

View full text Add to dashboard Cite

Glycosylphosphatidylinositols (GPIs) need to interact with other components in the cell membrane to transduce transmembrane signals. A bifunctional GPI probe was employed for photoaffinity‐based proximity labelling and identification of GPI‐interacting proteins in the cell membrane. This probe contained the entire core structure of GPIs and was functionalized with photoreactive diazirine and clickable alkyne to facilitate its crosslinking with proteins and attachment of an affinity tag. It was disclosed that this probe was more selective than our previously reported probe containing only a part structure of the GPI core for cell membrane incorporation and an improved probe for studying GPI‐cell membrane interaction. Eighty‐eight unique membrane proteins, many of which are related to GPIs/GPI‐anchored proteins, were identified utilizing this probe. The proteomics dataset is a valuable resource for further analyses and data mining to find new GPI‐related proteins and signalling pathways. A comparison of these results with those of our previous probe provided direct evidence for the profound impact of GPI glycan structure on its interaction with the cell membrane.

show abstract

Binding of pro-prion to filamin A disrupts cytoskeleton and correlates with poor prognosis in pancreatic cancer

Cited by 91 publications

References 67 publications

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility

EGFR and Prion protein promote signaling via FOXO3a‐KLF5 resulting in clinical resistance to platinum agents in colorectal cancer

Investigation of Glycosylphosphatidylinositol (GPI)‐Plasma Membrane Interaction in Live Cells and the Influence of GPI Glycan Structure on the Interaction

Contact Info

Product

Resources

About