Tazarotene-Induced Gene 1 (TIG1) Interacts with Serine Protease Inhibitor Kazal-Type 2 (SPINK2) to Inhibit Cellular Invasion of Testicular Carcinoma Cells

被引：17

作者：

Shyu, Rong-Yaun ^{[1
]}

Wang, Chun-Hua ^{[2
,3
]}

Wu, Chang-Chieh ^{[4
]}

Wang, Lu-Kai ^{[5
]}

Chen, Mao-Liang ^{[6
]}

Kuo, Chan-Yen ^{[6
]}

Lee, Ming-Cheng ^{[6
]}

Lin, Yi-Ying ^{[6
]}

Tsai, Fu-Ming ^{[6
]}

机构：

[1] Buddhist Tzuchi Med Fdn, Taipei Tzuchi Hosp, Dept Internal Med, New Taipei 231, Taiwan

[2] Buddhist Tzuchi Med Fdn, Taipei Tzuchi Hosp, Dept Dermatol, New Taipei 231, Taiwan

[3] Tzu Chi Univ, Sch Med, Hualien 970, Taiwan

[4] Triserv Gen Hosp, Natl Def Med Ctr, Keelung Branch, Dept Surg, Keelung 202, Taiwan

[5] Chang Gung Univ, Chang Gung Mem Hosp, Inst Radiol Res, Radiat Biol Core Lab, Taoyuan 333, Taiwan

[6] Buddhist Tzuchi Med Fdn, Taipei Tzuchi Hosp, Dept Res, New Taipei 231, Taiwan

来源：

BIOMED RESEARCH INTERNATIONAL | 2019年 / 2019卷

关键词：

ACID RECEPTOR-BETA; PLASMINOGEN-ACTIVATOR; DNA METHYLATION; TRYPSIN-INHIBITOR; CANCER; UPA; EXPRESSION; METASTASIS; PAI-1;

D O I：

10.1155/2019/6171065

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Tazarotene-induced gene 1 (TIG1) encodes a protein that is a retinoid-regulated tumor suppressor. TIG1 is expressed in most normal tissues, and downregulation of TIG1 expression in multiple cancers is caused by promoter hypermethylation. Kazal-type serine protease inhibitor-2 (SPINK2) is a serine protease inhibitor, and the SPINK protein family has been shown to inhibit the expression of urokinase-type plasminogen activator (uPA). In addition, increased levels of uPA and the uPA receptor were observed in testicular cancer tissues. This study demonstrated that TIG1 interacts with SPINK2 in NT2/D1 testicular carcinoma cells. TIG1 and SPINK2 were highly expressed in normal testis tissues, while low expression levels of TIG1 and SPINK2 were found in testicular cancer tissues. TIG1 inhibited cell invasion, migration, and epithelial-mesenchymal transition (EMT) of NT2/D1 cells. SPINK2 enhanced TIG1-regulated uPA activity and EMT suppression, while silencing SPINK2 alleviated TIG1-mediated EMT regulation, cell migration, and invasion. Therefore, the results suggest that the interaction between TIG1 and SPINK2 plays an important role in the inhibition of testicular cancer cell EMT, and suppression is mediated through downregulation of the uPA/uPAR signaling pathway.

引用

页数：10

共 36 条

[1] An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: Relationship to cystatins and the tumor suppressor TIG1 [J].

Aagaard, A ;

Listwan, P ;

Cowieson, N ;

Huber, T ;

Ravasi, T ;

Wells, CA ;

Flanagan, JU ;

Kellie, S ;

Hume, DA ;

Kobe, B ;

Martin, JL .

STRUCTURE, 2005, 13 (02) :309-317

[2] The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses [J].

Azouz, Nurit P. ;

Ynga-Durand, Mario A. ;

Caldwell, Julie M. ;

Jain, Ayushi ;

Rochman, Mark ;

Fischesser, Demetria M. ;

Ray, Leanne M. ;

Bedard, Mary C. ;

Mingler, Melissa K. ;

Forney, Carmy ;

Eilerman, Matthew ;

Kuhl, Jonathan T. ;

He, Hua ;

Myers, Jocelyn M. Biagini ;

Mukkada, Vincent A. ;

Putnam, Philip E. ;

Hershey, Gurjit K. Khurana ;

Kottyan, Leah C. ;

Wen, Ting ;

Martin, Lisa J. ;

Rothenberg, Marc E. .

SCIENCE TRANSLATIONAL MEDICINE, 2018, 10 (444)

[3] The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer [J].

Banys-Paluchowski, Malgorzata ;

Witzel, Isabell ;

Aktas, Bahriye ;

Fasching, Peter A. ;

Hartkopf, Andreas ;

Janni, Wolfgang ;

Kasimir-Bauer, Sabine ;

Pantel, Klaus ;

Schoen, Gerhard ;

Rack, Brigitte ;

Riethdorf, Sabine ;

Solomayer, Erich-Franz ;

Fehm, Tanja ;

Mueller, Volkmar .

SCIENTIFIC REPORTS, 2019, 9 (1)

[4] Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells [J].

Cai, Shengyun ;

Zhang, Pei ;

Dong, Suhe ;

Li, Li ;

Cai, Jianming ;

Xu, Mingjuan .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 45 (03) :1061-1071

[5] Aberrant TIG1 methylation associated with its decreased expression and clinicopathological significance in hepatocellular carcinoma [J].

Chen, Xi-Hua ;

Wu, Wen-Guang ;

Ding, Jian .

TUMOR BIOLOGY, 2014, 35 (02) :967-971

[6] Serine Protease Inhibitor Kazal Type 1 (SPINK1) Promotes Proliferation of Colorectal Cancer Through the Epidermal Growth Factor as a Prognostic Marker [J].

Chen, Yi-Ting ;

Tsao, Shu-Chuan ;

Yuan, Shyng-Shiou F. ;

Tsai, Hung-Pei ;

Chai, Chee-Yin .

PATHOLOGY & ONCOLOGY RESEARCH, 2015, 21 (04) :1201-1208

[7] uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies [J].

Duffy, Michael J. ;

McGowan, Patricia M. ;

Harbeck, Nadia ;

Thomssen, Christoph ;

Schmitt, Manfred .

BREAST CANCER RESEARCH, 2014, 16 (04)

[8] A novel discriminant score based on tumor-associated trypsin inhibitor for accurate diagnosis of metastasis in patients with breast cancer [J].

El-mezayen, Hatem A. ;

Metwally, Fatheya M. ;

Darwish, Hossam .

TUMOR BIOLOGY, 2014, 35 (03) :2759-2767

[9] New insights into the functional mechanisms and clinical applications of the kallikrein-related peptidase family [J].

Emami, Nashmil ;

Diamandis, Eleftherios P. .

MOLECULAR ONCOLOGY, 2007, 1 (03) :269-287

[10] Serine protease inhibitor kazal-type 6 inhibits tumorigenesis of human hepatocellular carcinoma cells via its extracellular action [J].

Ge, Kuikui ;

Huang, Jinjiang ;

Wang, Wei ;

Gu, Meigang ;

Dai, Xinchuan ;

Xu, Yuqiang ;

Wu, Hongyu ;

Li, Guodong ;

Lu, Hairong ;

Zhong, Jiang ;

Huang, Qingshan .

ONCOTARGET, 2017, 8 (04) :5965-5975

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