ArticleCancer letters2010
Raf kinase inhibitor protein suppresses nuclear factor-κB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression.
Article in Cancer letters, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 83 citations in OpenAlex.
- RKIP overexpression reduces lung adenocarcinoma aggressiveness and sensitizes cells to EGFR-targeted therapies.Molecular oncology · 2025Article
- NF2-Related Schwannomatosis (NF2): Molecular Insights and Therapeutic Avenues.International journal of molecular sciences · 2024Review
- Changes in Expression of Tumor Suppressor Gene RKIP Impact How Cancers Interact with Their Complex Environment.Cancers · 2023Review
- Article
- Virtual screening of PEBP1 inhibitors by combining 2D/3D-QSAR analysis, hologram QSAR, homology modeling, molecular docking analysis, and molecular dynamic simulations.Journal of molecular modeling · 2022Article
- Review
- The RhoA dependent anti-metastatic function of RKIP in breast cancer.Scientific reports · 2021Article
- PEBP1 suppresses HIV transcription and induces latency by inactivating MAPK/NF-κB signaling.EMBO reports · 2020Article
- Article
- LncRNA GATA6-AS1 Inhibits the Progression of Non-Small Cell Lung Cancer via Repressing microRNA-543 to Up-Regulating RKIP.Cancer management and research · 2020Article
- NF-κB Inhibition Suppresses Experimental Melanoma Lung Metastasis.Journal of cancer science and clinical therapeutics · 2020Article
- Overexpression of Raf-1 kinase inhibitor protein inhibits cell invasion and migration in lung cancer cells through suppressing epithelial-mesenchymal transition.Translational cancer research · 2019Article
- Current Status of Raf Kinase Inhibitor Protein (RKIP) in Lung Cancer: Behind RTK Signaling.Cells · 2019Review
- RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact.Cancers · 2018Review
- RKIP and peroxiredoxin 2 expression predicts the proliferative potential of gastric cancer stem cells.Oncology letters · 2018Article
- Raf Kinase Inhibitor Protein (RKIP) Inhibits Tumor Necrosis Factor-α (TNF-α) Induced Adhesion Molecules Expression in Vascular Smooth Muscle Bells by Suppressing (Nuclear Transcription Factor-κB (NF-kappaB) Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Overexpression of RKIP and its cross-talk with several regulatory gene products in multiple myeloma.Journal of experimental & clinical cancer research : CR · 2017Review
- Inhibition of pancreatic cancer cell migration by plasma anthocyanins isolated from healthy volunteers receiving an anthocyanin-rich berry juice.European journal of nutrition · 2017Article
- Downregulation of RIKP by miR-200a promotes the invasive ability of esophageal cancer cells by upregulating the expression of LIN28 and MMP-14.International journal of clinical and experimental pathology · 2017Article
- Effects of Raf kinase inhibitor protein expression on pancreatic cancer cell growth and motility: an in vivo and in vitro study.Journal of cancer research and clinical oncology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Accumulating evidence suggests that Raf kinase inhibitor protein (RKIP), which negatively regulates multiple signaling cascades including the Raf and nuclear factor-κB (NF-κB) pathways, functions as a metastasis suppressor. However, the basis for this activity is not clear. We investigated this question in a panel of breast cancer, colon cancer and melanoma cell lines. We found that RKIP negatively regulated the invasion of the different cancer cells through three-dimensional extracellular matrix barriers by controlling the expression of matrix metalloproteinases (MMPs), particularly, MMP-1 and MMP-2. Silencing of RKIP expression resulted in a highly invasive phenotype and dramatically increased levels of MMP-1 and MMP-2 expression, while overexpression of RKIP decreased cancer cell invasion in vitro and metastasis in vivo of murine tumor allografts. Knockdown of MMP-1 or MMP-2 in RKIP-knockdown cells reverted their invasiveness to normal. In contrast, when examining migration of the different cancer cells in a two-dimensional, barrier-less environment, we found that RKIP had either a positive regulatory activity or no activity, but in no case a negative one (as would be expected if RKIP suppressed metastasis at the level of cell migration itself). Therefore, RKIP's function as a metastasis suppressor appears to arise from its ability to negatively regulate expression of specific MMPs, and thus invasion through barriers, and not from a direct effect on the raw capacity of cells to move. The NF-κB pathway, but not the Raf pathway, appeared to positively control the invasion of breast cancer cells. A regulatory loop involving an opposing relationship between RKIP and the NF-κB pathway may control the level of MMP expression and cell invasion.
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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.