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p130Cas induces bone invasion by oral squamous cell carcinoma by regulating tumor epithelial–mesenchymal transition and cell proliferation.

Authors :
Yaginuma, Tatsuki
Gao, Jing
Nagata, Kengo
Muroya, Ryusuke
Fei, Huang
Nagano, Haruki
Chishaki, Sakura
Matsubara, Takuma
Kokabu, Shoichiro
Matsuo, Kou
Kiyoshima, Tamotsu
Yoshioka, Izumi
Jimi, Eijiro
Source :
Carcinogenesis. Aug2020, Vol. 41 Issue 8, p1038-1048. 11p.
Publication Year :
2020

Abstract

Bone invasion is a critical factor in determining the prognosis of oral squamous cell carcinoma (OSCC) patients. Transforming growth factor β (TGF-β) is abundantly expressed in the bone matrix and is involved in the acquisition of aggressiveness by tumors. TGF-β is also important to cytoskeletal changes during tumor progression. In this study, we examined the relationship between TGF-β signaling and cytoskeletal changes during bone invasion by OSCC. Immunohistochemical staining of OSCC samples from five patients showed the expression of p130Cas (Crk-associated substrate) in the cytoplasm and phosphorylated Smad3 expression in the nucleus in OSCC cells. TGF-β1 induced the phosphorylation of Smad3 and p130Cas, as well as epithelial–mesenchymal transition (EMT) accompanied by the downregulation of the expression of E-cadherin, a marker of epithelial cells, and the upregulation of the expression of N-cadherin, or Snail, a marker of mesenchymal cells, in human HSC-2 cells and mouse squamous cell carcinome VII (SCCVII) cells. SB431542, a specific inhibitor of Smad2/3 signaling, abrogated the TGF-β1-induced phosphorylation of p130Cas and morphological changes. Silencing p130Cas using an short hairpin RNA (shRNA) or small interfering RNA in SCCVII cells suppressed TGF-β1-induced cell migration, invasion, EMT and matrix metalloproteinase-9 (MMP-9) production. Compared with control SCCVII cells, SCCVII cells with silenced p130Cas strongly suppressed zygomatic and mandibular destruction in vivo by reducing the number of osteoclasts, cell proliferation and MMP-9 production. Taken together, these results showed that the expression of TGF-β/p130Cas might be a new target for the treatment of OSCC bone invasion. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01433334
Volume :
41
Issue :
8
Database :
Academic Search Index
Journal :
Carcinogenesis
Publication Type :
Academic Journal
Accession number :
145239366
Full Text :
https://doi.org/10.1093/carcin/bgaa007