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IR@PKUHSC  > 北京大学口腔医学院  > 口腔病理科  > 期刊论文
学科主题: 口腔医学
题名:
Podoplanin promotes the invasion of oral squamous cell carcinoma in coordination with MT1-MMP and Rho GTPases
作者: Li, Yao-Yin; Zhou, Chuan-Xiang; Gao, Yan
关键词: Podoplanin ; invasion ; Cdc42/RhoA ; MT1-MMP ; oral squamous cell carcinoma
刊名: AMERICAN JOURNAL OF CANCER RESEARCH
发表日期: 2015
卷: 5, 期:2, 页:514-529
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: TUMOR INVASION ; CANCER ; EXPRESSION ; METALLOPROTEINASE ; INVADOPODIA ; PROGRESSION ; MECHANISMS ; MIGRATION ; CDC42 ; HEAD
英文摘要:

Podoplanin overexpression has been reported in various cancers, however, the precise mechanism for podoplanin to promote tumor progression remains elusive. In the present study, podoplanin overexpression was found associated with invasiveness both in OSCC tissues and cell lines. Moreover, the cell invasiveness increased with forced podoplanin expression and decreased when podoplanin was knockdown, indicating podoplanin-mediated cell invasion during OSCC progression. To further identify the role of podoplanin in tumor invasion, cell spreading and immunofluorescence assay were performed firstly. It was found that podoplanin knockdown caused an impaired cell spreading with reduced filopodia and the premature assembly of stress fibers while podoplanin overexpression induced an increase in cellular protrusions and stress fibers with extensive parallel bundles. Then, pull-down assays revealed forced podoplanin expression increased Cdc42 activity and reduced RhoA activity while podoplanin knockdown decreased Cdc42 and increased RhoA markedly. Moreover, a hierarchy of crosstalk between RhoA and Cdc42 was confirmed in podoplanin-mediated cell motility. On the other hand, a significant correlation between podoplanin and MT1-MMP expression in OSCCs was found both in vivo and in vitro, co-located in invasive cells and cellular protrusions. Furthermore, our data showed MT1-MMP knockdown significantly blocked the upregulation of cell motility by forced podoplanin expression, indicating that MT1-MMP played a role in podoplanin-mediated tumor invasion. To further confirm the interaction between RhoA/Cdc42 complex, MT1-MMP and podoplanin, co-precipitation experiments were performed. Both the co-precipitation of podoplanin with MT1-MMP and the podoplanin-induced specific binding of MT1-MMP to Cdc42 were found, and immunofluorescence revealed the co-location of podoplanin, MT1-MMP and Cdc42 at the plasma membrane and filopodia induced an increase in cellular protrusion and stress fibers formation. Moreover, MT1-MMP inhibition could partly rescue the increase of Cdc42 activity caused by forced podoplanin expression. Taken together, our data demonstrated a hierarchy of crosstalk between RhoA and Cdc42 was involved in podoplanin-mediated cytoskeleton remodeling and invasion; the co-location and co-ordination of podoplanin, Cdc42 and MT1-MMP in the invadopodia might induce cytoskeleton remodeling, ECM degradation and tumor invasion, while podoplanin-induced EMT may not be indispensible during OSCC progression.

语种: 英语
所属项目编号: 30973338
项目资助者: National Nature Science Foundation of China
WOS记录号: WOS:000352204800004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51184
Appears in Collections:北京大学口腔医学院_口腔病理科_期刊论文

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作者单位: Peking Univ, Sch & Hosp Stomatol, Dept Oral Pathol, Beijing 100081, Peoples R China

Recommended Citation:
Li, Yao-Yin,Zhou, Chuan-Xiang,Gao, Yan. Podoplanin promotes the invasion of oral squamous cell carcinoma in coordination with MT1-MMP and Rho GTPases[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2015,5(2):514-529.
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