Language：English   Publishing type：Research paper (scientific journal)  

Our previous study revealed that metastasis‑associated protein 1 (MTA1), which is expressed in vascular endothelial cells, acts as a tube formation promoting factor. The present study aimed to clarify the importance of MTA1 expression in tube formation using MTA1‑knockout (KO) endothelial cells (MTA1‑KO MSS31 cells). Tube formation was significantly suppressed in MTA1‑KO MSS31 cells, whereas MTA1‑overexpression MTA1‑KO MSS31 cells regained the ability to form tube‑like structures. In addition, western blotting analysis revealed that MTA1‑KO MSS31 cells showed significantly higher levels of phosphorylation of non‑muscle myosin heavy chain IIa, which resulted in suppression of tube formation. This effect was attributed to a decrease of MTA1/S100 calcium‑binding protein A4 complex formation. Moreover, inhibition of tube formation in MTA1‑KO MSS31 cells could not be rescued by stimulation with vascular endothelial growth factor (VEGF). These results demonstrated that MTA1 may serve as an essential molecule for angiogenesis in endothelial cells and be involved in different steps of the angiogenic process compared with the VEGF/VEGF receptor 2 pathway. The findings showed that endothelial MTA1 and its pathway may serve as promising targets for inhibiting tumor angiogenesis, further supporting the development of MTA1‑based antiangiogenic therapies.

DOI： 10.3892/mmr.2021.12527

Repository Public URL： https://hdl.handle.net/2324/7173588

Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

Sunitinib, a tyrosine kinase inhibitor, is among the first‑line treatments for metastatic or advanced stage renal cell carcinoma (RCC). However, patients with RCC develop resistance to sunitinib. We have previously demonstrated that lysosome‑associated membrane protein 2 (LAMP‑2), which has three splice variants with different functions (LAMP‑2A, LAMP‑2B, and LAMP‑2C), is involved in RCC. In the present study, we examined which splice variants of LAMP‑2 contributed to sunitinib resistance in RCC cells. In vitro analysis using ACHN, human RCC cell line, revealed that the IC50 of sunitinib was significantly increased by overexpression of LAMP‑2A and LAMP‑2B, but not LAMP‑2C (P<0.01). Kaplan‑Meier survival analysis using clinical samples revealed an association between shorter survival and high expression of LAMP‑2A and LAMP‑2B, but not LAMP‑2C, in patients with RCC treated with sunitinib (P=0.01). Furthermore, high expression of LAMP‑2A and LAMP‑2B in RCC revealed a weak to moderate inverse correlation with the tumor shrinkage rate and progression‑free survival, respectively. Thus, high expression of LAMP‑2A and LAMP‑2B contributed to the acquisition of sunitinib resistance, indicating that the expression of these two variants can predict the efficacy of sunitinib treatment in patients with RCC.

DOI： 10.3892/or.2020.7752

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/JPER.19-0385

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41388-019-0748-z

Language：Japanese  

Language：English  

Language：English  

Language：English  

Language：English