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

[1]

ALEXANDROW MG, 1995, CANCER RES, V55, P1452

[2] p130Cas: A key signalling node in health and disease [J].

Barrett, Angela ;

Pellet-Many, Caroline ;

Zachary, Ian C. ;

Evans, Ian M. ;

Frankel, Paul .

CELLULAR SIGNALLING, 2013, 25 (04) :766-777

[3] BCAR1, a human homologue of the adapter protein p130Cas, and antiestrogen resistance in breast cancer cells [J].

Brinkman, A ;

van der Flier, S ;

Kok, EM ;

Dorssers, LCJ .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (02) :112-120

[4] Early onset oral tongue cancer in the United States: A literature review [J].

Campbell, Benjamin R. ;

Netterville, James L. ;

Sinard, Robert J. ;

Mannion, Kyle ;

Rohde, Sarah L. ;

Langerman, Alexander ;

Kim, Young J. ;

Lewis, James S., Jr. ;

Kuhs, Krystle A. Lang .

ORAL ONCOLOGY, 2018, 87 :1-7

[5] Tumor cell intravasation [J].

Chiang, Serena P. H. ;

Cabrera, Ramon M. ;

Segall, Jeffrey E. .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2016, 311 (01) :C1-C14

[6] Targeting TGF-β Signaling in Cancer [J].

Colak, Selcuk ;

ten Dijke, Peter .

TRENDS IN CANCER, 2017, 3 (01) :56-71

[7] Selective inhibition of NF-κB suppresses bone invasion by oral squamous cell carcinoma in vivo [J].

Furuta, Hiroyuki ;

Osawa, Kenji ;

Shin, Masashi ;

Ishikawa, Ayataka ;

Matsuo, Kou ;

Khan, Masud ;

Aoki, Kazuhiro ;

Ohya, Keiichi ;

Okamoto, Masato ;

Tominaga, Kazuhiro ;

Takahashi, Tetsu ;

Nakanishi, Osamu ;

Jimi, Eijiro .

INTERNATIONAL JOURNAL OF CANCER, 2012, 131 (05) :E625-E635

[8] Breaking down bone: new insight into site-specific mechanisms of breast cancer osteolysis mediated by metalloproteinases [J].

Guise, Theresa A. .

GENES & DEVELOPMENT, 2009, 23 (18) :2117-2123

[9] Cancer metastasis:: Building a framework [J].

Gupta, Gaorav P. ;

Massague, Joan .

CELL, 2006, 127 (04) :679-695

[10]

Ikebe T, 1998, INT J CANCER, V77, P578

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