Down-regulation of tensin2 enhances tumorigenicity and is associated with a variety of cancers
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Shiao-Ya Hong1,*, Yi-Ping Shih1,*, Peng Sun1, Wang-Ju Hsieh1, Wen-Chang Lin2, Su Hao Lo1
1Department of Biochemistry and Molecular Medicine, University of California-Davis, Sacramento, CA 95817, USA
2Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
*These authors have contributed equally to this work
Su Hao Lo, e-mail: [email protected]
Keywords: tensin, IRS1, Mek, focal adhesion, tumorigenesis
Received: January 4, 2016 Accepted: April 28, 2016 Published: May 17, 2016
Tensin family members, including tensin2 (TNS2), are present as major components of the focal adhesions. The N-terminal end of TNS2 contains a C1 region (protein kinase C conserved region 1) that is not found in other tensin members. Three isoforms of TNS2 have been identified with previous reports describing the shortest V3 isoform as lacking the C1 region. Although TNS2 is known to regulate cell proliferation and migration, its role in tumorigenicity is controversial. By gain-of-function overexpression approaches, results supporting either promotion or reduction of cancer cell tumorigenicity were reported. Here we report that the complete V3 isoform also contains the C1 region and describe the expression patterns of the three human TNS2 isoforms. By loss-of-function approaches, we show that silencing of TNS2 up-regulates the activities of Akt, Mek, and IRS1, and increases tumorigenicities in A549 and Hela cells. Using public database analyses we found that TNS2 is down-regulated in head and neck, esophageal, breast, lung, liver, and colon cancer. In addition, patients with low TNS2 expression showed poor relapse-free survival rates for breast and lung cancers. These results strongly suggest a role of tensin2 in suppressing cell transformation and reduction of tumorigenicity.
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