We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Regulation of Oral Squamous Cell Carcinoma Proliferation Through Crosstalk Between SMAD7 and CYLD.
- Authors
Wei-Li Ge; Jun-Feng Xu; Jun Hu
- Abstract
Background/Aims: SMAD7 is a key inhibitor of transforming growth factor β (TGFβ) receptor signaling, which regulates the alteration of cancer cell invasiveness through epithelialmesenchymal cell conversion. Dysfunction of protein ubiquitination plays a critical role in carcinogenesis, whereas the involvement a deubiquitinating enzyme, cylindromatosis gene (CYLD), in the tumor invasion of oral squamous cell carcinoma (OSCC) is unknown. Methods: Here, we studied the role of CYLD in regulation of OSCC cell invasion, using clinic specimens and cell lines. We modified SMAD7 levels in OSCC cells, and examined its effects on CYLD mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified CYLD levels in OSCC cells, and examined its effects on SMAD7 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in CYLD and/or SMAD7-modified OSCC cells in a transwell cell invasion assay. Results: We found that the levels of CYLD and SMAD7 were significantly decreased in OSCC specimens, compared to the paired normal tissue. Metastatic OSCC appeared to contained lower levels of CYLD and SMAD7. Moreover, CYLD and SMAD7 levels strongly correlated in OSCC specimens. Low CYLD levels were associated with poor patients' survival. Moreover, SMAD did not regulate CYLD, but CYLD regulated the levels of SMAD7 in OSCC cells. Furthermore, CYLD overexpression inhibited SMAD7-mediated cell invasion, while CYLD depletion increased SMAD7-mediated cell invasion in OSCC cells. Conclusion: Suppression of CYLD in OSCC cells may promote SMAD7-mediated cancer invasion. Thus, CYLD appears to be an intriguing therapeutic target to prevent OSCC metastases.
- Subjects
CANCER treatment; SQUAMOUS cell carcinoma; ORAL cancer; CANCER cell proliferation; SMAD proteins; TRANSFORMING growth factor receptors; CANCER invasiveness; CELLULAR signal transduction; BIOLOGICAL crosstalk; PREVENTION
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2016, Vol 38, Issue 5, p1209
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000443069