Role of ATF5 in the invasive potential of diverse human cancer cell lines

Nukuda, Akihiro; Endoh, Hiroki; Yasuda, Motoaki; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

doi:10.1016/j.bbrc.2016.04.131

Cited by 27 publications

(22 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some of uORF-containing genes, such as ATF5 and DDIT3, were also subject to DDX3-mediated translation control. ATF5 knockdown indeed disrupted cell invasion in diverse cancer cell lines (36). Thus, DDX3 is able to multiply its effect on activating a specific axis of ATF4 signaling to promote cell invasion (Fig.…”

Section: Discussionmentioning

confidence: 84%

DDX3 Activates CBC-eIF3–Mediated Translation of uORF-Containing Oncogenic mRNAs to Promote Metastasis in HNSCC

Chen

Yang³

et al. 2018

Cancer Research

View full text Add to dashboard Cite

Mutated or dysregulated participates in the progression and metastasis of cancer via its multiple roles in regulating gene expression and cellular signaling. Here, we show that the high expression levels of DDX3 in head and neck squamous cell carcinoma (HNSCC) correlate with lymph node metastasis and poor prognosis and demonstrate that DDX3 is essential for the proliferation, invasion, and metastasis of oral squamous cell carcinoma (OSCC) cells. Microarray analyses revealed that DDX3 is required for the expression of a set of pro-metastatic genes, including ATF4-modulated genes in an aggressive OSCC cell line. DDX3 activated translation of and a set of its downstream targets, all of which contain upstream open reading frames (uORF). DDX3 promoted translation of these targets, likely by skipping the inhibitory uORF. DDX3 specifically enhanced the association of the cap-binding complex (CBC) with uORF-containing mRNAs and facilitated recruitment of the eukaryotic initiation factor 3 (eIF3). CBC and certain eIF3 subunits contributed to the expression of metastatic-related gene expression. Taken together, our results indicate a role for the novel DDX3-CBC-eIF3 translational complex in promoting metastasis. The discovery of DDX3-mediated expression of oncogenic uORF-containing genes expands knowledge on translational control mechanisms and provides potential targets for cancer therapy. http://cancerres.aacrjournals.org/content/canres/78/16/4512/F1.large.jpg .

show abstract

Section: Discussionmentioning

confidence: 84%

DDX3 Activates CBC-eIF3–Mediated Translation of uORF-Containing Oncogenic mRNAs to Promote Metastasis in HNSCC

Chen

Yang³

et al. 2018

Cancer Research

View full text Add to dashboard Cite

show abstract

“…In contrast, the marked reduction in the activation of PI3K/Akt signaling pathway, as evidenced by decreased p-Akt levels, may indicate a reduced proliferation rate of ATF5-KD mammary tumor cells. Importantly, previous studies, investigating the role of ATF5 in survival of breast cancer cell lines, have focused so far on experiments performed in vitro , such as proliferation, migration, and apoptosis assays, and intracellular mechanisms by which ATF5 may exert its effects (16, 22, 28, 29). Therefore, to our knowledge, we show here for the first time that ATF5 downregulation leads to a decreased mammary tumor growth in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…Very few studies have reported the association between ATF5 expression and cell motility. Among them, Nukuda et al performed an invasion assay in highly invasive cell lines, such as human HT-1080 fibrosarcoma, A549 lung cancer, and MDA-MB-231 breast cancer, and revealed that ATF5 knockdown reduces the invasiveness of these cells (29). Moreover, the authors showed that ATF5 expression was markedly increased in the invasive MDA-MB-231 cells than in the less invasive breast cancer cell line, MCF-7.…”

Section: Discussionmentioning

confidence: 99%

Activating Transcription Factor-5 Knockdown Reduces Aggressiveness of Mammary Tumor Cells and Attenuates Mammary Tumor Growth

et al. 2017

View full text Add to dashboard Cite

Activating transcription factor-5 (ATF5) is an anti-apoptotic factor and has been implicated in enhancing the survival of cancer cells under stress and in regulating the autophagy process. Targeting ATF5 in anticancer therapy may be particularly attractive because of its differential role in cancer cells than in non-transformed cells, thus allowing specificity of the treatment. Using the delivery of short hairpin RNA vectors into the Mvt1 and Met1 cell lines, we tested the role of ATF5 in the development of mammary tumors in vivo and in regulating proliferation and migration of these cells in vitro. In this study, we demonstrate that knockdown of ATF5 (ATF5-KD) in both cell lines results in a decreased tumor volume and weight, as well as in a reduced proliferation rate and migratory potential of the cells. In addition, ATF5-KD led to an increased autophagy flux and a shift in the sub-populations comprising Mvt1 cells from the aggressive CD24-positive cells toward less aggressive CD24-negative cells. Taken together, these findings suggest that ATF5 plays an important role in enhancing mammary tumor cells overall aggressiveness and in promoting mammary tumor growth and emphasize the possible benefit of anti-ATF5 therapy in breast cancer patients, particularly, against tumors characterized with the positive expression of cell surface CD24.

show abstract

“…ATF5 also regulates growth and metabolism coordinating factors such as EGR1, mTOR and FGF21, as well as the mitochondrial-protective genes outlined above [59, 101–103]. In addition to pro-growth and anti-apoptotic phenotypes, ATF5 contributes the resistance to radiotherapy [81] and the invasiveness of tumor cells by inducing integrin-α2 and integrin-β1 [96]. …”

Section: The Uprmt and Cancermentioning

confidence: 99%

Mitochondrial dysfunction in cancer: Potential roles of ATF5 and the mitochondrial UPR

Deng

Haynes

2017

Seminars in Cancer Biology

View full text Add to dashboard Cite

Mitochondria form a cellular network of organelles, or cellular compartments, that efficiently couple nutrients to energy production in the form of ATP. As cancer cells rely heavily on glycolysis, historically mitochondria and the cellular pathways in place to maintain mitochondrial activities were thought to be more relevant to diseases observed in non-dividing cells such as muscles and neurons. However, more recently it has become clear that cancers rely heavily on mitochondrial activities including lipid, nucleotide and amino acid synthesis, suppression of mitochondria-mediated apoptosis as well as oxidative phosphorylation (OXPHOS) for growth and survival. Considering the variety of conditions and stresses that cancer cell mitochondria may incur such as hypoxia, reactive oxygen species and mitochondrial genome mutagenesis, we examine potential roles for a mitochondrial-protective transcriptional response known as the mitochondrial unfolded protein response (UPRmt) in cancer cell biology.

show abstract

Role of ATF5 in the invasive potential of diverse human cancer cell lines

Cited by 27 publications

References 20 publications

DDX3 Activates CBC-eIF3–Mediated Translation of uORF-Containing Oncogenic mRNAs to Promote Metastasis in HNSCC

DDX3 Activates CBC-eIF3–Mediated Translation of uORF-Containing Oncogenic mRNAs to Promote Metastasis in HNSCC

Activating Transcription Factor-5 Knockdown Reduces Aggressiveness of Mammary Tumor Cells and Attenuates Mammary Tumor Growth

Mitochondrial dysfunction in cancer: Potential roles of ATF5 and the mitochondrial UPR

Contact Info

Product

Resources

About