An Activating Transcription Factor 5-Mediated Survival Pathway as a Target for Cancer Therapy

Sheng, Zhi; Evans, Sara K.; Green, Michael R.

doi:10.18632/oncotarget.180

Cited by 18 publications

(6 citation statements)

References 19 publications

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“…Moreover ATF5 promotes proliferation of cerebral cortical neuroprogenitor cells and is required for terminal differentiation and survival of olfactory sensory neurons [ 22 ]. In addition several studies have previously demonstrated that ATF5 is highly expressed in a variety of tumors [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Potential Role of Activating Transcription Factor 5 during Osteogenesis

Vicari¹,

Calabrese²,

Forte³

et al. 2015

Stem Cells International

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Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB) family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2), encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

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Section: Introductionmentioning

confidence: 99%

Potential Role of Activating Transcription Factor 5 during Osteogenesis

Vicari¹,

Calabrese²,

Forte³

et al. 2015

Stem Cells International

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“…Cell lysates were made in ice-cold 1X RIPA buffer (MilliporeSigma) containing 1 mmol/L phenylmethylsulfonyl fluoride (MilliporeSigma) and protease inhibitor cocktail (MilliporeSigma; refs. 14 , 19 ). Cell lysates were sonicated for 10 seconds (three times), and the protein concentration of each sample was measured using the Bio-Rad Protein Assay.…”

Section: Methodsmentioning

confidence: 99%

Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance

Banerjee,

Boboila,

Okochi

et al. 2023

Cancer Research Communications

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MYCN-amplified neuroblastoma often presents as a highly aggressive metastatic disease with a poor prognosis. Activating transcription factor 5 (ATF5) is implicated in neural cell differentiation and cancer cell survival. Here, we show that ATF5 is highly expressed in patients with stage 4 high-risk neuroblastoma, with increased expression correlating with a poorer prognosis. We demonstrated that ATF5 promotes the metastasis of neuroblastoma cell lines in vivo. Functionally, ATF5 depletion significantly reduced xenograft tumor growth and metastasis of neuroblastoma cells to the bone marrow and liver. Mechanistically, ATF5 endows tumor cells with resistance to anoikis, thereby increasing their survival in systemic circulation and facilitating metastasis. We identified the proapoptotic BCL-2 modifying factor (BMF) as a critical player in ATF5-regulated neuroblastoma anoikis. ATF5 suppresses BMF under suspension conditions at the transcriptional level, promoting anoikis resistance, whereas BMF knockdown significantly prevents ATF5 depletion–induced anoikis. Therapeutically, we showed that a cell-penetrating dominant-negative ATF5 peptide, CP-d/n-ATF5, inhibits neuroblastoma metastasis to the bone marrow and liver by inducing anoikis sensitivity in circulating tumor cells. Our study identified ATF5 as a metastasis promoter and CP-d/n-ATF5 as a potential antimetastatic therapeutic agent for neuroblastoma. Significance: This study shows that resistance to anoikis in neuroblastoma is mediated by ATF5 and offers a rationale for targeting ATF5 to treat metastatic neuroblastoma.

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“…Hyperactivated Ras regulates many oncogenic pathways in several human cancers, including glioblastoma, the most infiltrating, aggressive, and poorly treated brain tumor. Huang et al synthesized apolipoprotein E3-reconstituted high-density lipoprotein (ApoE-rHDL) encapsulated calcium phosphate (CaP) nanoparticle core, named as CaP-rHDL [103], for tumor-targeting siRNA delivery, activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma [104,105]. They investigated in vivo tumor-targeting efficiency of CaP-rHDL and its cellular uptake through micropinocytosis in intracranial C6 and GICs glioblastoma-bearing mice models, and observed an efficient delivery of ATF5 siRNA to Ras-activated brain cancer cells [103].…”

Section: Ras Pathwaymentioning

confidence: 99%

Aberrant Signaling Pathways in Cancer Cells: Application of Nanomaterials

2021

Journal of Cellular Signaling

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Cell signaling pathways involve several proteins, called kinases, to pass on vital messages from the transmembrane-proteins, e.g., receptor tyrosine kinases (RTKs) to the nucleus of a cell through a cascade of processes for various activities such as controlled cell division, proliferation, apoptosis, metabolism, DNA replication and repair. Alterations in these signaling proteins combined with genetic and/or epigenetic mutations spawn various types of cancer that empowers the cells to ignore or maneuver the immune signals and carry on felonious activities such as uncontrolled cell division and growth, genetic instability, angiogenesis around the tumor in hypoxia, eluding the body's immune system, cell migration, and invasion of surrounding healthy cells. Inhibition of such malicious transmuted signaling pathways has therapeutic importance for cancer. In this article, we have briefly described three vital signaling pathways that are aberrantly triggered by Ras and Wnt proteins and the NF-2 genes causing different types of cancer. Recent research in the targeted therapy using drugs to put off these signaling pathways, especially, for cancer stem cells (CSCs) has been reviewed here. However, such therapy suffers a low success rate due to the resistance to drugs by cancer cells. Considering this snag of targeting drugs, many researchers use nanoparticles for this purpose; some of these works have been reviewed in brief. The consequences of protein-nanoparticles interaction in this approach has also been discussed. Finally, we have proposed use of nanomaterials for targeted ion delivery, or targeted heating using light or magnetic field, to destroy cancer cells.

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An Activating Transcription Factor 5-Mediated Survival Pathway as a Target for Cancer Therapy

Abstract: ABSTRACT:Genes

Cited by 18 publications

References 19 publications

Potential Role of Activating Transcription Factor 5 during Osteogenesis

Potential Role of Activating Transcription Factor 5 during Osteogenesis

Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance

Aberrant Signaling Pathways in Cancer Cells: Application of Nanomaterials

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