ArticleMolecular cancer2011
Ribosomal protein S6 kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein.
Article in Molecular cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Article
- Discovery of a novel RSK2 inhibitor for the treatment of metastatic pancreatic cancer.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- Targeting RSK2 in Cancer Therapy: A Review of Natural Products.Anti-cancer agents in medicinal chemistry · 2025Review
- Review
- A network map of macrophage-stimulating protein (MSP) signaling.Journal of cell communication and signaling · 2023Article
- Article
- RON, ROR1 and SUSD2 expression in tissues of endometrial carcinoma patients. Clinicopathological and prognostic implications.Contemporary oncology (Poznan, Poland) · 2022Article
- RON in hepatobiliary and pancreatic cancers: Pathogenesis and potential therapeutic targets.World journal of gastroenterology · 2021Review
- Recepteur d'origine nantais contributes to the development of endometriosis via promoting epithelial-mesenchymal transition of a endometrial epithelial cells.Journal of cellular and molecular medicine · 2021Article
- RON Mediates Tumor-Promoting Effects in Endometrial Adenocarcinoma.BioMed research international · 2021Article
- Macrophage-Stimulating Protein Enhances Osteoblastic Differentiation via the Recepteur d'Origine Nantais Receptor and Extracellular Signal-Regulated Kinase Signaling Pathway.Journal of bone metabolism · 2020Article
- Therapeutic efficacy of a novel humanized antibody-drug conjugate recognizing plexin-semaphorin-integrin domain in the RON receptor for targeted cancer therapy.Journal for immunotherapy of cancer · 2019Article
- The High Mobility Group A1 (HMGA1) Chromatin Architectural Factor Modulates Nuclear Stiffness in Breast Cancer Cells.International journal of molecular sciences · 2019Article
- Silencing of COPB2 inhibits the proliferation of gastric cancer cells and induces apoptosis via suppression of the RTK signaling pathway.International journal of oncology · 2019Article
- Therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate Zt/g4-MMAE targeting RON receptor tyrosine kinase for cancer therapy.Journal for immunotherapy of cancer · 2019Article
- Tumor-secreted Pros1 inhibits macrophage M1 polarization to reduce antitumor immune response.The Journal of clinical investigation · 2018Article
- mTORC1 is a key mediator of RON-dependent breast cancer metastasis with therapeutic potential.NPJ breast cancer · 2018Article
- RON and c-Met facilitate metastasis through the ERK signaling pathway in prostate cancer cells.Oncology reports · 2017Article
- Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery.Journal of cancer research and clinical oncology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundEpithelial to mesenchymal transition (EMT) occurs during cancer cell invasion and malignant metastasis. Features of EMT include spindle-like cell morphology, loss of epithelial cellular markers and gain of mesenchymal phenotype. Activation of the RON receptor tyrosine kinase by macrophage-stimulating protein (MSP) has been implicated in cellular EMT program; however, the major signaling determinant(s) responsible for MSP-induced EMT is unknown.
resultsThe study presented here demonstrates that RSK2, a downstream signaling protein of the Ras-Erk1/2 pathway, is the principal molecule that links MSP-activated RON signaling to complete EMT. Using MDCK cells expressing RON as a model, a spindle-shape based screen was conducted, which identifies RSK2 among various intracellular proteins as a potential signaling molecule responsible for MSP-induced EMT. MSP stimulation dissociated RSK2 with Erk1/2 and promoted RSK2 nuclear translocation. MSP strongly induced RSK2 phosphorylation in a dose-dependent manner. These effects relied on RON and Erk1/2 phosphorylation, which is significantly potentiated by transforming growth factor (TGF)-β1, an EMT-inducing cytokine. Specific RSK inhibitor SL0101 completely prevented MSP-induced RSK phosphorylation, which results in inhibition of MSP-induced spindle-like morphology and suppression of cell migration associated with EMT. In HT-29 cancer cells that barely express RSK2, forced RSK2 expression results in EMT-like phenotype upon MSP stimulation. Moreover, specific siRNA-mediated silencing of RSK2 but not RSK1 in L3.6pl pancreatic cancer cells significantly inhibited MSP-induced EMT-like phenotype and cell migration.
conclusionsMSP-induced RSK2 activation is a critical determinant linking RON signaling to cellular EMT program. Inhibition of RSK2 activity may provide a therapeutic opportunity for blocking RON-mediated cancer cell migration and subsequent invasion.
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