ArticleOncogene2015
Transcriptional repression of IFNβ1 by ATF2 confers melanoma resistance to therapy.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- A multigene support vector machine predictor for metastasis of cutaneous melanoma.Molecular medicine reports · 2018Pooled it
- Article
- Genome-Wide Analysis of lncRNA-mRNA Co-Expression Networks in CD133+/CD44+ Stem-like PDAC Cells.Cancers · 2023Article
- Article
- The two-faced role of ATF2 on cisplatin response in gastric cancer depends on p53 context.Cell & bioscience · 2022Article
- NLRP1 Functions Downstream of the MAPK/ERK Signaling via ATF4 and Contributes to Acquired Targeted Therapy Resistance in Human Metastatic Melanoma.Pharmaceuticals (Basel, Switzerland) · 2020Article
- The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression.Cancer cell international · 2020Article
- Exosomal microRNA-26b-5p down-regulates ATF2 to enhance radiosensitivity of lung adenocarcinoma cells.Journal of cellular and molecular medicine · 2020Article
- Transcriptomic Features of T Cell-Barren Tumors Are Conserved Across Diverse Tumor Types.Frontiers in immunology · 2020Article
- Stress and interferon signalling-mediated apoptosis contributes to pleiotropic anticancer responses induced by targeting NGLY1.British journal of cancer · 2018Article
- Downregulation of histone demethylase JMJD1C inhibits colorectal cancer metastasis through targeting ATF2.American journal of cancer research · 2018Article
- Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways.Cell death & disease · 2017Article
- MicroRNA-451 regulates chemoresistance in renal cell carcinoma by targeting ATF-2 gene.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer.Cell death & disease · 2017Article
- ATF2, a paradigm of the multifaceted regulation of transcription factors in biology and disease.Pharmacological research · 2017Review
- The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation.Science signaling · 2015Article
Corrections and comments
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Authors and funding
21 authors at 8 institutions in 2 countries.
Funding
Abstract
The resistance of melanoma to current treatment modalities represents a major obstacle for durable therapeutic response, and thus the elucidation of mechanisms of resistance is urgently needed. The crucial functions of activating transcription factor-2 (ATF2) in the development and therapeutic resistance of melanoma have been previously reported, although the precise underlying mechanisms remain unclear. Here, we report a protein kinase C-ɛ (PKCɛ)- and ATF2-mediated mechanism that facilitates resistance by transcriptionally repressing the expression of interferon-β1 (IFNβ1) and downstream type-I IFN signaling that is otherwise induced upon exposure to chemotherapy. Treatment of early-stage melanomas expressing low levels of PKCɛ with chemotherapies relieves ATF2-mediated transcriptional repression of IFNβ1, resulting in impaired S-phase progression, a senescence-like phenotype and increased cell death. This response is lost in late-stage metastatic melanomas expressing high levels of PKCɛ. Notably, nuclear ATF2 and low expression of IFNβ1 in melanoma tumor samples correlates with poor patient responsiveness to biochemotherapy or neoadjuvant IFN-α2a. Conversely, cytosolic ATF2 and induction of IFNβ1 coincides with therapeutic responsiveness. Collectively, we identify an IFNβ1-dependent, cell-autonomous mechanism that contributes to the therapeutic resistance of melanoma via the PKCɛ-ATF2 regulatory axis.
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