Identification of a peptide that interacts with Nestin protein expressed in brain cancer stem cells

Beck, Samuel J.; Jin, Xun; Yin, Jinlong; Kim, Sung Hak; Lee, Nam Kyung; Oh, Seungmin; Jin, Xiong; Kim, Minkook; Son, Jee Soo; Kim, Sung Chan; Nam, Do Hyun; Kim, Se Hyuk; Kang, Soo‐Kyung; Kim, Hyunggee; Choi, Yun Jaie

doi:10.1016/j.biomaterials.2011.07.048

Cited by 42 publications

(29 citation statements)

References 32 publications

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“…Breast CSC express Nestin and are crucial for the development and progression of breast cancer [35]. To understand how Nestin regulates the proliferation and migration of breast CSC, we analyzed the expression of Nestin in ESA + CD44 + CD24 − lineage − CSC.…”

Section: Resultsmentioning

confidence: 99%

Nestin positively regulates the Wnt/β-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells

et al. 2014

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IntroductionWe investigated Nestin expression in triple-negative breast cancer and examined how the modulation of Nestin expression affects cell cycle progression, survival, invasion and regulatory signaling in breast cancer stem cells (CSC) in vitro.MethodsNestin expression in 150 triple-negative breast cancer specimens were examined by immunohistochemistry. The role of Nestin expression in tumorigenesis was examined by assaying naturally occurring Nestinhigh/Nestinlow CSC from 12 breast cancer tissues, as well as CSC from 26 clinical specimens, where Nestin overexpression and silencing was achieved by genetic manipulation, for their ability to form mammospheres and induce solid tumors. Cell cycle progression, spontaneous apoptosis and invasiveness of Nestin-silenced breast CSC were investigated by flow cytometry and transwell assays. The relative levels of expression of epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway-related molecules were determined by western blotting.ResultsNestin expression was significantly associated with poor survival in patients with triple-negative breast cancer (P = 0.01). Nestinhigh breast CSC rapidly formed typical mammospheres in vitro. Nestinhigh, but not Nestinlow CSC, efficiently formed solid tumors in vivo. Nestin silencing induced cell cycle arrest at G2/M (52.03% versus 19.99% in controls) and promoted apoptosis (36.45% versus 8.29% in controls). Nestin silencing also inhibited breast CSC invasiveness, and was associated with significantly upregulated E-cadherin, while N-cadherin, vimentin, a-smooth muscle actin (a-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression was downregulated (P <0.05 for all). Nestin silencing also upregulated Axin, glycogen synthase kinase-3 beta (GSK-3β), adenomatous polyposis coli (APC), and peroxisome proliferator-activated receptor alpha (PPARa), and downregulated β-catenin, c-Myc, cyclin D and MMP-7 expression in CSC. Inhibition of the Wnt/β-catenin pathway mitigated mammosphere formation in Nestinhigh CSC, while inhibition of GSK-3β promoted the mammosphere formation in Nestinlow CSC (P <0.05 for all).ConclusionsOur data indicates that Nestin positively regulates the proliferation, survival and invasiveness of breast CSC by enhancing Wnt/β-catenin activation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0408-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Nestin positively regulates the Wnt/β-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells

et al. 2014

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“…Unfortunately, the inability of this peptide to cross the plasma membrane has hindered investigations of its anticancer potential. In contrast, a peptide binding to nestin that was identified through phage display screening 84 had the ability to cross the plasma membrane. When injected into glioma-bearing mice, this peptide accumulated in nestin-positive glioma cells but did not appear to affect tumor growth.…”

Section: Identifying If-specific Drugsmentioning

confidence: 93%

Roles and Potential Clinical Applications of Intermediate Filament Proteins in Brain Tumors

Quick

Paul

Skalli

2015

Seminars in Pediatric Neurology

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“…Recently, Beck and colleagues (Beck, Jin et al 2011) used phage display to screen peptide libraries for ligands that preferentially bind to their targets in the gliomas (Pasqualini and Ruoslahti 1996). They identified a stem cell-targeting (GSCT) 'AQYLNPS' peptide that selectively binds to the N-terminal isotype(s) of nestin, an intermediate filament protein found exclusively in neural precursor cells (Lendahl, Zimmerman et al 1990) and surprisingly expressed in undifferentiated glioblastoma BTSCs (Beck, Jin et al 2011).…”

Section: Diagnostic Approach To Identify Btscsmentioning

confidence: 99%

“…They identified a stem cell-targeting (GSCT) 'AQYLNPS' peptide that selectively binds to the N-terminal isotype(s) of nestin, an intermediate filament protein found exclusively in neural precursor cells (Lendahl, Zimmerman et al 1990) and surprisingly expressed in undifferentiated glioblastoma BTSCs (Beck, Jin et al 2011). Interestingly, the GSCT peptide effectively penetrated glioblastoma tissue to target nestin+ BTSCs in vitro (Beck, Jin et al 2011). However, given the fact that nestin is not universally expressed in BTSCs, the GSCT peptide may only be targeting a subpopulation of BTSCs that express nestin.…”

Section: Diagnostic Approach To Identify Btscsmentioning

confidence: 99%

Brain Tumor Treatment: 2017 Update

Chakraborty¹,

Han²,

Faltas³

et al. 2018

CCO

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Malignant brain tumors are a heterogeneous group of diseases arising from different cell types that affect both adults and children. The high recurrence rate of malignant brain tumors typically is due to reappearance of focal masses, indicating that a sub population of tumor cells are insensitive to current therapies and may be responsible for reinitiating tumor growth. It is generally agreed that the resistant tumor cells are comprised of cancer stem cells or tumor-initiating cells. While brain tumor stem cells (BTSCs) were first isolated within the last decade, much of the early research has been focused on identifying the BTSC markers and therapeutic targets. The challenge however, is to translate this knowledge to therapeutics. In the current review, we survey the remedial strategies to target BTSCs, which includes diagnostic, pharmacologic, immunologic, viral, and post-transcriptional approaches.

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Identification of a peptide that interacts with Nestin protein expressed in brain cancer stem cells

Cited by 42 publications

References 32 publications

Nestin positively regulates the Wnt/β-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells

Nestin positively regulates the Wnt/β-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells

Roles and Potential Clinical Applications of Intermediate Filament Proteins in Brain Tumors

Brain Tumor Treatment: 2017 Update

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