IR@PKUHSC  > 北京大学口腔医学院  > 口腔病理科
学科主题口腔医学
Podoplanin promotes the invasion of oral squamous cell carcinoma in coordination with MT1-MMP and Rho GTPases
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
2015
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
WOS记录号WOS:000352204800004
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51184
专题北京大学口腔医学院_口腔病理科
作者单位Peking Univ, Sch & Hosp Stomatol, Dept Oral Pathol, Beijing 100081, Peoples R China
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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.
APA Li, Yao-Yin,Zhou, Chuan-Xiang,&Gao, Yan.(2015).Podoplanin promotes the invasion of oral squamous cell carcinoma in coordination with MT1-MMP and Rho GTPases.AMERICAN JOURNAL OF CANCER RESEARCH,5(2),514-529.
MLA Li, Yao-Yin,et al."Podoplanin promotes the invasion of oral squamous cell carcinoma in coordination with MT1-MMP and Rho GTPases".AMERICAN JOURNAL OF CANCER RESEARCH 5.2(2015):514-529.
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