ArticleAnnals of surgical oncology2022
Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9.
Article in Annals of surgical oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 5 citations in OpenAlex.
- Role of lipid-associated fibroblasts and their signature genes FABP4, CD36 and ABCA8 in gastric cancer progression.Oncology letters · 2026Article
- Downregulation of Roundabout guidance receptor 2 suppresses hepatocellular carcinoma progression by interacting with Y-box binding protein 1.Scientific reports · 2024Article
- LncRNA AL645608.3 mediates malignant progression of acute myeloid leukemia.American journal of translational research · 2024Article
- Iron overload induces cerebral endothelial senescence in aged mice and in primary culture in a sex-dependent manner.Aging cell · 2023Article
- Development of a basement membrane gene signature and identification of the potential candidate therapeutic targets for pancreatic cancer.Gland surgery · 2023Article
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18 authors at 1 institution in 1 country.
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Abstract
backgroundThe axon guidance gene family, SLIT/ROBO pathway, controls neural network formation, which correlates with the development of several cancers.
methodsWe found through analysis of the public database that ROBO4, one of the axon guidance molecules among the SLIT/ROBO family, is significantly downregulated in primary pancreatic cancer tissues compared with adjacent normal tissues. We carried out transfection experiments using three pancreatic cancer cell lines (MiaPaCa-2, BxPC-3, and SW1990) and one pancreatic duct epithelial cell line (HPDE6c7). A total of 51 clinical samples were then examined by immunohistochemical staining to find an association between ROBO4 expression at the protein level, clinical characteristics, and surgical outcomes.
resultsROBO4 overexpression suppressed the invasion and migration abilities in MiaPaCa-2 and BxPC-3, while ROBO4 siRNA transfection to SW1990 and HPDE6c7 enhanced those activities. PCR-based profiling detected MMP-9 as a candidate downstream target of ROBO4, which was validated by decreased MMP-9 activity after the ROBO4 overexpression assay. High ROBO4 expression clinical samples had significantly better overall survival rather than low ROBO4 cases (P = 0.048).
conclusionThese findings suggest that decreased ROBO4 expression activates malignant phenotypes in cancer cells and is correlated with poor survival outcomes in pancreatic cancer.
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