ArticleThe Journal of biological chemistry2013
The prometastatic ribosomal S6 kinase 2-cAMP response element-binding protein (RSK2-CREB) signaling pathway up-regulates the actin-binding protein fascin-1 to promote tumor metastasis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Cadmium Exposure Facilitates Oral Squamous Cell Carcinoma Progression and Epithelial-mesenchymal Transition Through the Upregulation of ATP1B4.Biological trace element research · 2026Article
- Targeting RSK2 enhances the efficacy of IGF1R inhibitor against triple-negative breast cancer via antagonizing IGF1/IGF1R signaling mediated by GATA3-IGFBP5 pathway.Acta pharmacologica Sinica · 2026Article
- The Role of Actin-Binding Proteins in Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2026Review
- Non-canonical dihydrolipoyl transacetylase promotes chemotherapy resistance via mitochondrial tetrahydrofolate signaling.Nature communications · 2025Article
- Fascin-1 in Cancer Cell Metastasis: Old Target-New Insights.International journal of molecular sciences · 2023Review
- Succinyl-CoA ligase ADP-forming subunit beta promotes stress granule assembly to regulate redox and drive cancer metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- Article
- Activation of the CREB Coactivator CRTC2 by Aberrant Mitogen Signaling promotes oncogenic functions in HPV16 positive head and neck cancer.Neoplasia (New York, N.Y.) · 2022Article
- Transcriptome analysis reveals the potential biological function of FSCN1 in HeLa cervical cancer cells.PeerJ · 2022Article
- Fascin-1: Updated biological functions and therapeutic implications in cancer biology.BBA advances · 2022Review
- The role of fascin-1 in the pathogenesis, diagnosis and management of respiratory related cancers.Frontiers in oncology · 2022Review
- FSCN1 acts as a promising therapeutic target in the blockade of tumor cell motility: a review of its function, mechanism, and clinical significance.Journal of Cancer · 2022Review
- Review
- Fascin actin-bundling protein 1 in human cancer: promising biomarker or therapeutic target?Molecular therapy oncolytics · 2021Review
- Review
- p90 ribosomal S6 kinase (RSK) phosphorylates myosin phosphatase and thereby controls edge dynamics during cell migration.The Journal of biological chemistry · 2019Article
- Inhibition of Breast Cancer Cell Invasion by Ras Suppressor-1 (RSU-1) Silencing Is Reversed by Growth Differentiation Factor-15 (GDF-15).International journal of molecular sciences · 2019Article
- MAST1 Drives Cisplatin Resistance in Human Cancers by Rewiring cRaf-Independent MEK Activation.Cancer cell · 2018Article
- High Expression Levels of Fascin-1 Protein in Human Gliomas and its Clinical Relevance.Open medicine (Warsaw, Poland) · 2018Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Metastasis is the leading cause of death in patients with breast, lung, and head and neck cancers. However, the molecular mechanisms underlying metastases in these cancers remain unclear. We found that the p90 ribosomal S6 kinase 2 (RSK2)-cAMP response element-binding protein (CREB) pathway is commonly activated in diverse metastatic human cancer cells, leading to up-regulation of a CREB transcription target Fascin-1. We also observed that the protein expression patterns of RSK2 and Fascin-1 correlate in primary human tumor tissue samples from head and neck squamous cell carcinoma patients. Moreover, knockdown of RSK2 disrupts filopodia formation and bundling in highly invasive cancer cells, leading to attenuated cancer cell invasion in vitro and tumor metastasis in vivo, whereas expression of Fascin-1 significantly rescues these phenotypes. Furthermore, targeting RSK2 with the small molecule RSK inhibitor FMK-MEA effectively attenuated the invasive and metastatic potential of cancer cells in vitro and in vivo, respectively. Taken together, our findings for the first time link RSK2-CREB signaling to filopodia formation and bundling through the up-regulation of Fascin-1, providing a proinvasive and prometastatic advantage to human cancers. Therefore, protein effectors of the RSK2-CREB-Fascin-1 pathway represent promising biomarkers and therapeutic targets in the clinical prognosis and treatment of metastatic human cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.