ABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
Smad4, a common-mediator of Smads, plays a central role in forming complexes with receptor-phosphorylated Smads, and then transduces transforming growth factor (TGF)-ß signals into the nuclei. Although many cellular factors are involved in TGF-ß induced epithelial-to-mesenchymal transition (EMT) and cell migration, very little is known with the mechanism of Smad4 regulation on pro-oncogenes response by TGF-ß. Herein, we demonstrate the interaction of Sentrin-specific protease 2 (SENP2) with Smad4 through SENP2 residue 363~400. The same segment is also important for desumoylation of Smad4, and able to relieve sumoylation-mediated TGF-ß repression. The SENP2363~400 segment is critical for TGF-ß-induced cell migration, which is correlated with SENP2363~400 deletion mutant failed to increase matrix metalloproteinase (MMP)-9 and EMT marker gene expression. Moreover, our results suggest that the interaction and desumoylation between SENP2 and Smad4 promote cell migration in triple-negative breast cancer cells. Altogether, our data show how SENP2 regulates its substrate for desumoylation, and also the role of SENP2 in TGF-ß induced cancer cell migration.
Subject(s)
Carcinogenesis/metabolism , Carcinogenesis/pathology , Cysteine Endopeptidases/metabolism , Cell Movement , Humans , Protein Binding , Signal Transduction/drug effects , Smad4 Protein/metabolism , Spheroids, Cellular/metabolism , Spheroids, Cellular/pathology , Substrate Specificity , Sumoylation , Transforming Growth Factor betaABSTRACT
BACKGROUND AND PURPOSE: To examine the effect of thermal stimulation (TS) on upper extremity (UE) motor recovery in patients at least 3 months after stroke. METHODS: Participants were randomly assigned to either the experimental group or the control group. In addition to regular rehabilitation programs, the experimental group received an UE-TS protocol for 30 minutes per day (3 days/week for 8 weeks); the control group received the same TS protocol on lower extremity. The UE subscale of the Stroke Rehabilitation Assessment of Movement and the Action Research Arm Test were primary outcome measures. The Modified Ashworth Scale and the Barthel Index were secondary outcome measures. All measures were administered at baseline, after TS, and at 1-month follow-up. RESULTS: Twenty-three participants (12 in the experimental group) completed the study. After treatment, the experimental group showed significant improvement compared to the control group in the scores of the UE subscale of the Stroke Rehabilitation Assessment of Movement and Action Research Arm Test. At follow-up examination, a significant improvement in the experimental group was observed on the UE subscale of the Stroke Rehabilitation Assessment of Movement. CONCLUSIONS: The 8-week additional UE-TS protocol improved UE motor recovery for stroke patients 3 months after onset.