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
© 2022. Society of Surgical Oncology..
BACKGROUND: The axon guidance gene family, SLIT/ROBO pathway, controls neural network formation, which correlates with the development of several cancers.
METHODS: We 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.
RESULTS: ROBO4 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).
CONCLUSION: These findings suggest that decreased ROBO4 expression activates malignant phenotypes in cancer cells and is correlated with poor survival outcomes in pancreatic cancer.
| Errataetall: |
CommentIn: Ann Surg Oncol. 2022 Oct;29(11):7190-7191. - PMID 35767102 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Annals of surgical oncology - 29(2022), 11 vom: 20. Okt., Seite 7180-7189 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yamanaka, Masaya [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Completed 23.09.2022 Date Revised 13.12.2023 published: Print-Electronic CommentIn: Ann Surg Oncol. 2022 Oct;29(11):7190-7191. - PMID 35767102 Citation Status MEDLINE |
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| doi: |
10.1245/s10434-022-12039-5 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a 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 |
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| 500 | |a Date Completed 23.09.2022 | ||
| 500 | |a Date Revised 13.12.2023 | ||
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| 500 | |a CommentIn: Ann Surg Oncol. 2022 Oct;29(11):7190-7191. - PMID 35767102 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. Society of Surgical Oncology. | ||
| 520 | |a BACKGROUND: The axon guidance gene family, SLIT/ROBO pathway, controls neural network formation, which correlates with the development of several cancers | ||
| 520 | |a METHODS: We 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 | ||
| 520 | |a RESULTS: ROBO4 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) | ||
| 520 | |a CONCLUSION: These 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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| 700 | 1 | |a Sakai, Akihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Mii, Shinji |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Daigo |e verfasserin |4 aut | |
| 700 | 1 | |a Kurimoto, Keisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Nobutake |e verfasserin |4 aut | |
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