ArticleOncogene2021
A novel HDGF-ALCAM axis promotes the metastasis of Ewing sarcoma via regulating the GTPases signaling pathway.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
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- Integrated Analysis of Immune-Related Genes Reveals Altered Biological Functions and Immune Cell Abundance in Sleep DeprivationEndocrine, metabolic & immune disorders drug targets · 2026Article
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- Erythroid progenitor cell-mediated spleen-tumor interaction deteriorates cancer immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HDGF Knockout Suppresses Colorectal Cancer Progression and Drug Resistance by Modulating the DNA Damage Response.Biomolecules · 2025Article
- CD6 in Human Disease.Cells · 2025Review
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Ligands of CD6: roles in the pathogenesis and treatment of cancer.Frontiers in immunology · 2024Review
- Prognostic value ofHeliyon · 2023Article
- BLM promotes malignancy in PCa by inducing KRAS expression and RhoA suppression via its interaction with HDGF and activation of MAPK/ERK pathway.Journal of cell communication and signaling · 2023Article
- Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway.Oncogene · 2023Article
- Identification of Factors Driving Doxorubicin-Resistant Ewing Tumor Cells to Survival.Cancers · 2022Article
- Self-Assembly of a Multifunction DNA Tetrahedron for Effective Delivery of Aptamer PL1 andACS applied materials & interfaces · 2022Article
- Pan-cancer analysis of oncogenic role of Programmed Cell Death 2 Like (PDCD2L) and validation in colorectal cancer.Cancer cell international · 2022Article
- Elevated ALCAM Expression Associated with Endotypes and Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps.Journal of inflammation research · 2022Article
- The dual role of CD6 as a therapeutic target in cancer and autoimmune disease.Frontiers in medicine · 2022Review
- The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers.Cancers · 2021Review
- Roles for growth factors and mutations in metastatic dissemination.Biochemical Society transactions · 2021Review
- Prognosis Implication of a Novel Metabolism-Related Gene Signature in Ewing Sarcoma.Journal of oncology · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ewing sarcoma (ES) is a type of highly aggressive pediatric tumor in bones and soft tissues and its metastatic spread remains the most powerful predictor of poor outcome. We previously identified that the transcription factor hepatoma-derived growth factor (HDGF) promotes ES tumorigenesis. However, the mechanisms underlying ES metastasis remain unclear. Here, we show that HDGF drives ES metastasis in vitro and in vivo, and HDGF reduces metastasis-free survival (MFS) in two independent large cohorts of human ES patients. Integrative analyses of HDGF ChIP-seq and gene expression profiling in ES cells reveal that HDGF regulates multiple metastasis-associated genes, among which activated leukocyte cell adhesion molecule (ALCAM) emerges as a major HDGF target and a novel metastasis-suppressor in ES. HDGF down-regulates ALCAM, induces expression and activation of the downstream effectors Rho-GTPase Rac1 and Cdc42, and promotes actin cytoskeleton remodeling and cell-matrix adhesion. In addition, repression of ALCAM and activation of Rac1 and Cdc42 are required for the pro-metastatic functions of HDGF in vitro. Moreover, analyses in murine models with ES tumor orthotopic implantation and experimental metastasis, as well as in human ES samples, demonstrate the associations among HDGF, ALCAM, and GTPases expression levels. Furthermore, high HDGF/low ALCAM expression define a subgroup of patients harboring the worst MFS. These findings suggest that the HDGF/ALCAM/GTPases axis represents a promising therapeutic target for limiting ES metastasis.
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