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

被引：11

作者：

Yaginuma, Tatsuki ^{[1
,2
,3
]}

Gao, Jing ^{[3
]}

Nagata, Kengo ^{[4
]}

Muroya, Ryusuke ^{[3
]}

Fei, Huang ^{[3
]}

Nagano, Haruki ^{[3
]}

Chishaki, Sakura ^{[5
]}

Matsubara, Takuma ^{[1
]}

Kokabu, Shoichiro ^{[1
]}

Matsuo, Kou ^{[6
]}

Kiyoshima, Tamotsu ^{[4
]}

Yoshioka, Izumi ^{[2
]}

Jimi, Eijiro ^{[1
,3
,5
]}

机构：

[1] Kyushu Dent Univ, Div Mol Signaling & Biochem, Dept Hlth Improvement, Kokurakita Ku, 2-6-1 Manazuru, Kitakyushu, Fukuoka 8038580, Japan

[2] Kyushu Dent Univ, Div Oral Med, Dept Oral & Maxillofacial Reconstruct Surg, Kokurakita Ku, 2-6-1 Manazuru, Kitakyushu, Fukuoka 8038580, Japan

[3] Kyushu Univ, Fac Dent Sci, Lab Mol & Cellular Biochem, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[4] Kyushu Univ, Fac Dent Sci, Div Maxillofacial Diagnost & Surg Sci, Lab Oral Pathol,Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[5] Kyushu Univ, Fac Dent Sci, Oral Hlth Brain Hlth Total Hlth Res Ctr, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[6] Kyushu Dent Univ, Dept Hlth Improvement, Div Oral Pathol, Kokurakita Ku, 2-6-1 Manazuru, Kitakyushu, Fukuoka 8038580, Japan

来源：

CARCINOGENESIS | 2020年 / 41卷 / 08期

基金：

日本学术振兴会;

关键词：

GROWTH-FACTOR-BETA; TGF-BETA; BREAST-CANCER; PARATHYROID-HORMONE; E-CADHERIN; EXPRESSION; PROTEIN; PROGRESSION; INHIBITION; CATENIN;

D O I：

10.1093/carcin/bgaa007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Bone invasion is a critical factor in determining the prognosis of oral squamous cell carcinoma (OSCC) patients. Transforming growth factor beta (TGF-beta) is abundantly expressed in the bone matrix and is involved in the acquisition of aggressiveness by tumors. TGF-beta is also important to cytoskeletal changes during tumor progression. In this study, we examined the relationship between TGF-beta 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-beta 1 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-beta 1-induced phosphorylation of p130Cas and morphological changes. Silencing p130Cas using an short hairpin RNA (shRNA) or small interfering RNA in SCCVII cells suppressed TGF-beta 1-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-beta/p130Cas might be a new target for the treatment of OSCC bone invasion.

引用

页码：1038 / 1048

页数：11

共 40 条

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