Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK-ERK Pathway
| Autor: | Eric Wun-Hao Lu, Ko-Hsiu Lu, Hsiao-Ju Chu, Chia-Hsuan Chou, Jia-Sin Yang, Shun-Fa Yang, Chiao-Wen Lin, Yi-Hsien Hsieh |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Cancer Research Gene knockdown Kinase Chemistry Activator (genetics) medicine.medical_treatment Cell Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell migration medicine.disease Article LCN2 medicine.anatomical_structure Cytokine Oncology osteosarcoma medicine Cancer research MET Osteosarcoma metastasis RC254-282 |
| Zdroj: | Cancers Cancers, Vol 13, Iss 3181, p 3181 (2021) Volume 13 Issue 13 |
| ISSN: | 2072-6694 |
| Popis: | Simple Summary Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was decreased by LCN2 knockdown. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the mitogen-activated protein kinases/ERK kinase (MEK)–ERK pathway. Abstract Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, using RNA sequencing technology, we found that LCN2 repressed MET gene expression in U2OS cells. Manipulation of LCN2 levels influenced the migratory potential of osteosarcoma cells as cellular migration was enhanced by transfecting with vectors containing a constitutively active LCN2 cDNA and recombinant human LCN2. Moreover, the phosphorylation of mitogen-activated protein kinases/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 and ERK 1/2 was decreased by LCN2 knockdown. Furthermore, the use of ERK inhibitor (U0126) and activator (tBHQ) confirmed that the pharmaceutic inhibition of MEK–ERK augmented the LCN2-mediated MET suppression and migration of U2OS and HOS cells. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the MEK–ERK pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|