Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway

被引:35
作者
Wen, Gengyun [1 ]
Hong, Mei [1 ,2 ]
Li, Bingyan [1 ,3 ]
Liao, Wupeng [4 ]
Cheng, Simon K. [4 ]
Hu, Burong [1 ]
Calaf, Gloria M. [1 ,5 ]
Lu, Ping [1 ]
Partridge, Michael A. [1 ]
Tong, Jian [3 ]
Hei, Tom K. [1 ,3 ,4 ,6 ]
机构
[1] Columbia Univ, Ctr Radiol Res, Coll Phys & Surg, Med Ctr, New York, NY 10032 USA
[2] S China Agr Univ, Coll Life Sci, Guangzhou, Guangdong, Peoples R China
[3] Soochow Univ, Sch Radiat Med & Publ Hlth, Suzhow, Peoples R China
[4] Columbia Univ, Coll Phys & Surg, Med Ctr, Dept Radiat Oncol, New York, NY USA
[5] Univ Tarapaca, Inst Alta Invest, Arica, Chile
[6] Columbia Univ, Med Ctr, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA
基金
美国国家卫生研究院;
关键词
TGFBI; metastasis; extracellular matrix; adhesion-mediated signaling; mouse model; TUMORIGENIC PHENOTYPE; BETAIG-H3; GENE; BETA-IG-H3; ASBESTOS; CANCER; MTOR; METASTASIS; APOPTOSIS; AKT/PKB; KINASE;
D O I
10.3892/ijo.2011.1097
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
As an uncommon cancer, mesothelioma is very hard to treat with a low average survival rate owing to its usual late detection and being highly invasive. The link between asbestos exposure and the development of mesothelioma in humans is unequivocal. TGFBI, a secreted protein that is induced by transforming growth factor-beta in various human cell types, has been shown to be associated with tumorigenesis in various types of tumors. It has been demonstrated that TGFBI expression is markedly suppressed in asbestos-induced tumorigenic cells, while an ectopic expression of TGFBI significantly suppresses tumorigenicity and progression in human bronchial epithelial cells. In order to delineate a potential role of TGFBI in mediating the molecular events that occur in mesothelioma tumorigenesis, we generated stable TGFBI knockdown mutants from the mesothelium cell line Met-5A by using an shRNA approach, and secondly created ectopic TGFBI overexpression mutants from the mesothelioma cell line H28 in which TGFBI is absent. We observed that in the absence of TGFBI, the knockdown mesothelial and mesothelioma cell lines exhibited an elevated proliferation rate, enhanced plating efficiency, increased anchorage-independent growth, as well as an increased cellular protein synthesis rate as compared with their respective controls. Furthermore, cell cycle regulatory proteins c-myc/cyclin D1/phosphor-Rb were upregulated; a more active PI3K/Akt/mTOR signaling pathway was also detected in TGFBI-depleted cell lines. These findings suggest that TGFBI may repress mesothelioma tumorigenesis and progression via the PI3K/Akt signaling pathway.
引用
收藏
页码:1001 / 1009
页数:9
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