ArticleOncogene2014
RKIP and HMGA2 regulate breast tumor survival and metastasis through lysyl oxidase and syndecan-2.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 99 citations in OpenAlex.
- Robust performance of a novel stool DNA test of methylated SDC2 for colorectal cancer detection: a multicenter clinical study.Clinical epigenetics · 2020Trial
- Article
- Hologenomic analysis of rectal mucus sampling for detection of adenomatous polyps and colorectal cancer.Nature communications · 2025Article
- Proteoglycans in Breast Cancer: Friends and Foes.Biomolecules · 2025Review
- The YYR (YY1- RKIP) Regulatory Axis in the pathogenesis of Cancer and Immune Evasion.Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting syndecan-2 inhibits papillary thyroid cancer invasiveness and de-differentiation.BMC endocrine disorders · 2025Article
- SDC2 and FN as cargo proteins in circulating extracellular vesicles in obese breast cancer patients with lymph node metastasis.Scientific reports · 2025Article
- SDC1 is a critical transmembrane proteoglycan in breast cancer.World journal of surgical oncology · 2025Review
- Combined Methylation Analysis of SDC2 and TFPI2 in Plasma: A Noninvasive Liquid Biopsy Approach for Early Detection of Colorectal Polyp.International journal of molecular and cellular medicine · 2025Article
- The emerging role and mechanism of HMGA2 in breast cancer.Journal of cancer research and clinical oncology · 2024Review
- The Significance of Human Papillomavirus Receptors Related Genetic Variants in Cervical Cancer Screening.Microbiology spectrum · 2023Article
- Revisiting the Syndecans: Master Signaling Regulators with Prognostic and Targetable Therapeutic Values in Breast Carcinoma.Cancers · 2023Review
- Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.Molecular cancer · 2023Review
- Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.Advances in cancer research · 2023Article
- Epithelial-to-Mesenchymal Transition Supports Ovarian Carcinosarcoma Tumorigenesis and Confers Sensitivity to Microtubule Targeting with Eribulin.Cancer research · 2022Article
- A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA.BMC gastroenterology · 2022Article
- Harnessing RKIP to Combat Heart Disease and Cancer.Cancers · 2022Review
- Research progress in breast cancer stem cells: characterization and future perspectives.American journal of cancer research · 2022Review
- The miRNA: a small but powerful RNA for COVID-19.Briefings in bioinformatics · 2021Review
- Targeting stromal cell Syndecan-2 reduces breast tumour growth, metastasis and limits immune evasion.International journal of cancer · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Elucidating targets of physiological tumor metastasis suppressors can highlight key signaling pathways leading to invasion and metastasis. To identify downstream targets of the metastasis suppressor Raf-1 kinase inhibitory protein (RKIP/PEBP1), we utilized an integrated approach based upon statistical analysis of tumor gene expression data combined with experimental validation. Previous studies from our laboratory identified the architectural transcription factor and oncogene, high mobility group AT-hook 2 (HMGA2), as a target of inhibition by RKIP. Here we identify two signaling pathways that promote HMGA2-driven metastasis. Using both human breast tumor cells and an MMTV-Wnt mouse breast tumor model, we show that RKIP induces and HMGA2 inhibits expression of miR-200b; miR-200b directly inhibits expression of lysyl oxidase (LOX), leading to decreased invasion. RKIP also inhibits syndecan-2 (SDC2), which is aberrantly expressed in breast cancer, via downregulation of HMGA2; but this mechanism is independent of miR-200. Depletion of SDC2 induces apoptosis and suppresses breast tumor growth and metastasis in mouse xenografts. RKIP, LOX and SDC2 are coordinately regulated and collectively encompass a prognostic signature for metastasis-free survival in ER-negative breast cancer patients. Taken together, our findings reveal two novel signaling pathways targeted by the metastasis suppressor RKIP that regulate remodeling of the extracellular matrix and tumor survival.
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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.