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Tankyrase: Function and Tankyrase Inhibitor in Cancer
Biomed Sci Letters 2018;24:150-156
Published online September 30, 2018;  https://doi.org/10.15616/BSL.2018.24.3.150
© 2018 The Korean Society For Biomedical Laboratory Sciences.

Mi Kyung Kim†,*

Department of Systems Biology, Yonsei University, Seoul 03722, Korea
Correspondence to: Mi Kyung Kim. Department of Systems Biology, Yonsei University, Seoul 03722, Korea. Tel: +82-2-2123-2709, Fax: +82-2-312-5657, e-mail: biokyung@gmail.com
Received May 28, 2018; Revised August 24, 2018; Accepted August 24, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract

Tankyrases are multifunctional poly (ADP-ribose) polymerases that regulate a variety of cellular processes including WNT signaling, telomere maintenance, regulation of mitosis, and many others. Tankyrases interact with target proteins and regulate their interactions and stability through poly (ADP-ribosyl) ation. In addition to their roles in telomere maintenance and regulation of mitosis, tankyrase proteins regulate tumor suppressors such as AXIN, PTEN, and AMOT. Therefore, tankyrases can be effective targets for cancer treatment. Tankyrase inhibitors could affect a variety of pathways that are carcinogenic (essential for the unlimited proliferation of human cancer cells), including WNT, AKT, YAP, telomere maintenance, and regulation of mitosis. Recently, new aspects of the function and mechanism of tankyrases have been reported and several tankyrase inhibitors have been identified. Also, it has been proposed that the combination of conventional chemotherapy agents with tankyrase inhibitors may have synergistic anti-cancer effects. Based on this, it is expected that more advanced and improved tankyrase inhibitors will be developed, enabling new therapeutic strategies against cancer and other tankyrase linked diseases. This review discusses tankyrase function and the role of tankyrase inhibitors in the treatment of cancer.

Keywords : Tankyrase, WNT signaling, Tankyrase inhibitor, XAV939
꽌濡

뤃由(ADP-由щ낫뒪) 뤃由щ㉧씪븘젣(PARP)뒗 떎뼇븳 꽭룷 諛 遺꾩옄 怨쇱젙뿉 愿뿬븯뒗 嫄곕떒諛깆쭏 怨꾩뿴씠떎. 씠 슚냼뒗 踰덉뿭 썑 蹂삎, 利 몴쟻떒諛깆쭏쓣 뤃由-ADP 由щ낫떎솕(PARsylated) (Bürkle et al., 2005; Riffell et al., 2012; Haikarainen et al., 2014)븯뿬 DNA 넀긽 닔由(Malanga et al., 2005), 꽭룷 뒪듃젅뒪 떊샇 쟾떖(Luo et al., 2012), 쑀쟾옄 쟾궗(Kraus et al., 2003; Yeh et al., 2007) 諛 끂솕(Beneke et al., 2007)瑜 룷븿븳 닔留롮 꽭룷 怨쇱젙쓣 議곗젅븳떎. Tankyrase 寃고빀떒諛깆쭏 6-amino acid tankyrase-binding motif (RxxAxG 삉뒗 RxxPxG 삉뒗 RxxxxG) (Huang et al., 2009; Guettler et al., 2011; Li et al., 2015)瑜 궗슜븯뿬 tankyrase 떒諛깆쭏怨 긽샇 옉슜븳떎. Tankyrase 떒諛깆쭏 telomere 쑀吏 蹂댁닔(Smith et al., 2000), WNT 떊샇(Huang et al., 2009), 쑀궗 遺꾩뿴(Chang et al., 2005; Chang et al., 2005; Kim et al., 2012, 2014), 룷룄떦궗(Guo et al., 2012; Ha et al., 2012), 쑀쟾꽦 吏덈퀝 泥대Ⅴ끂鍮뚯쬁(Guettler et al., 2011; Levaot et al., 2011) 벑 떎뼇븳 꽭룷 湲곕뒫뿉 愿뿬븳떎.

理쒓렐源뚯쓽 빆븫젣뒗 kinase inhibitor뿉 珥덉젏쓣 留욎텛뼱 媛쒕컻릺뿀쑝굹 씠윭븳 솕빀臾쇰뱾뿉 븳 遺옉슜뱾씠 蹂닿퀬릺硫댁꽌 깉濡쒖슫 쁺뿭뿉꽌쓽 源껋쓣 씠슜븳 빆븫젣쓽 媛쒕컻씠 슂援щ릺怨 엳떎. WNT 떊샇 쟾떖 寃쎈줈(WNT signaling pathway)뒗 諛곗븘 諛쒖깮, 議곗쭅 빆긽꽦 諛 留롮 吏덈퀝怨 뿰愿릺뼱 떎뼇븳 湲곕뒫쓣 닔뻾븯湲 븣臾몄뿉 WNT 떊샇 쟾떖 寃쎈줈瑜 議곗젅븷 닔 엳뒗 깉濡쒖슫 씤옄쓽 諛쒓껄 諛 씠쓽 議곗젅쓣 넻븳 빆븫젣쓽 媛쒕컻씠 슂援щ릺怨 엳떎. 鍮꾩젙긽쟻씤 WNT 떊샇 쟾떖 寃쎈줈쓽 솢꽦솕뒗 β-catenin 異뺤쟻쓣 빞湲곗떆耳 떎뼇븳 諛쒖븫 쑀쟾옄쓽 쟾궗瑜 珥됱쭊븯뿬 옣븫, 룓븫 벑쓽 諛쒕퀝怨 吏꾪뻾쓽 썝씤씠 맂떎(C.G.A., 2012; Nguyen et al., 2009; Pacheco-Pinedo et al., 2011). 理쒓렐 뿰援ъ뿉 뵲瑜대㈃ tankyrase 議곗젅뿉 쓽븳 WNT 떊샇 쟾떖 寃쎈줈쓽 뿰愿꽦씠 옣븫 꽭룷뿉꽌 엯利앸릺뿀怨, 씠뿉 諛뷀깢쑝濡 愿젴 빟臾 媛쒕컻씠 솢諛쒗엳 씠猷⑥뼱吏怨 엳떎(Wu et al., 2016). 삉븳, tankyrase媛 諛쒖븫 쑀쟾옄씤 YAP 醫낆뼇 뼲젣 씤옄씤 PTEN쓣 議곗젅븳떎뒗 蹂닿퀬媛 엳떎(Wang et al., 2015; Li et al., 2015; Wang et al., 2016).

蹂 끉臾몄뿉꽌뒗 tankyrase 븫 諛쒖깮 湲곗쟾怨쇱쓽 긽愿愿怨 諛 븫 移섎즺젣濡쒖꽌쓽 tankyrase inhibitor쓽 以묒슂꽦怨 쑀슜꽦쓣 냼媛쒗븯怨좎옄 븳떎.

蹂몃줎

Tankyrase 븫

Tankyrase 떒諛깆쭏 醫낆뼇 諛쒖깮 寃쎈줈(WNT, YAP, AKT), 뀛濡쒕몄뼱 쑀吏, 쑀궗 遺꾩뿴 벑쓣 룷븿븳 怨쇱젙뱾怨 뿰愿릺뼱 븫쓽 諛쒕퀝怨 吏꾪뻾쓣 議곗젅븳떎(Fig. 1).

Fig. 1.

Different biological tankyrase functions are relevant to cancer, including oncogenic pathways (WNT, YAP, and AKT), telomere maintenance, and regulation of mitosis.


醫낆뼇 諛쒖깮 寃쎈줈: Tankyrase뒗 醫낆뼇 諛쒖깮 寃쎈줈(WNT, YAP 諛 AKT) 뿰愿릺뼱 엳뒗뜲, WNT 떊샇 쟾떖 寃쎈줈뒗 븫쓣 룷븿븳 留롮 깮臾쇳븰쟻 怨쇱젙쓣 議곗젅븳떎(Clevers, 2006). WNT 떊샇 쟾떖 寃쎈줈뒗 adenomatous polyposis coli (APC), AXIN, glycogen synthase kinase 3β (GSK3β) (Rubinfeld et al., 1996)瑜 룷븿븳 β-catenin 遺꾪빐蹂듯빀泥댁뿉 쓽븳 썑냽諛섏쓳湲 β-catenin쓽 떒諛깆쭏 遺꾪빐瑜 議곗젅븳떎. GSK3β CKI뿉 쓽빐 씤궛솕맂 APC 떒諛깆쭏 β-catenin 遺꾪빐蹂듯빀泥대줈 쑀룄븳떎. AXIN 씠 遺꾪빐蹂듯빀泥닿 β-catenin 씤궛솕 諛 쑀鍮꾪댄떞솕媛 吏꾪뻾릺룄濡 븳떎. Tankyrase뿉 쓽븳 AXIN PARsylation 쑀鍮꾪댄떞-봽濡쒗뀒븘醫 寃쎈줈뿉 쓽븳 AXIN 遺꾪빐瑜 쑀룄븯怨, 씠뼱꽌 AXIN 遺꾪빐뒗 β-catenin 遺꾪빐蹂듯빀泥댁쓽 뙆愿대 쑀諛쒗븳떎. 諛⑹텧맂 β-catenin씠 빑쑝濡 씠룞븯怨 WNT 몴쟻 쑀쟾옄쓽 쟾궗 議곗젅쓣 솢꽦솕 븳떎(Huang et al., 2009). 醫낆뼇 뼲젣 씤옄씤 APC뒗 옣븫쓽 80% 씠긽뿉꽌 룎뿰蹂씠媛 씪뼱굹怨(C.G.A., 2012), tankyrase媛 WNT 떊샇 쟾떖 寃쎈줈瑜 議곗젅븯湲 븣臾몄뿉 tankyrase inhibitor뒗 옣븫뿉 빐 留ㅼ슦 쑀슜븯떎. 떎젣濡, tankyrase inhibition APC 룎뿰蹂씠 옣븫 꽭룷뿉꽌 WNT 떊샇 쟾떖 寃쎈줈 諛 醫낆뼇 꽦옣쓣 뼲젣븯怨(Huang et al., 2009; Waaler et al., 2012; Lau et al., 2013), WNT 떊샇 寃쎈줈쓽 李⑤떒쓣 넻빐 옣븫 꽭룷二쇱쓽 빆븫젣쓽 媛먯닔꽦쓣 利앷떆궓떎(Clevers, 2006). 삉븳, tankyrase inhibitor瑜 넻븳 WNT 떊샇 쟾떖 寃쎈줈쓽 湲명빆 옉슜 룓븫 꽭룷뿉 슚怨쇱쟻씠怨(Nguyen et al., 2009; Pacheco-Pinedo et al., 2011), tankyrase inhibitor媛 룓븫 꽭룷뿉꽌 빆 醫낆뼇 몴쟻쑝濡 옉슜븯뒗 삁媛 蹂닿퀬릺뿀떎(Casás-Selves et al., 2012; Busch et al., 2013).

YAP 諛쒖븫떒諛깆쭏(oncoprotein)怨 엳룷(Hippo) 떊샇 쟾떖 寃쎈줈쓽 빑떖 옉슜湲곕줈 븫뿉 愿뿬븯뒗 寃껋쑝濡 굹궗떎(Dong et al., 2007; Harvey et al., 2013; Mo et al., 2014). Angiomotin 怨꾩뿴쓽 떒諛깆쭏(AMOT) YAP 뼲젣 議곗젅옄씠떎(Wang et al., 2011). 理쒓렐쓽 뿰援ъ뿉 뵲瑜대㈃ tankyrase inhibition뒗 tankyrase 留ㅺ컻 angiomotin 떒諛깆쭏 遺꾪빐瑜 빐븯뿬 angiomotin 怨꾩뿴쓽 떒諛깆쭏쓣 븞젙솕떆궡쑝濡쒖뜥 YAP 醫낆뼇 諛쒖깮쓣 뼲젣븳떎뒗 寃껋쓣 蹂댁뿬 以떎(Wang et al., 2015; Wang et al., 2016). YAP 떊샇 쟾떖씠 RAF MEK 몴쟻 븫移섎즺踰뺤쓣 룷븿븳 빟臾 궡꽦뿉 愿뿬븿씠 엯利앸릺뿀怨(Lin et al., 2015), tankyrase inhibitor뿉 쓽븳 EGFR 꽦옣 뼲젣 利앷媛 蹂닿퀬릺뿀떎(Wang et al., 2016). 씠윭븳 뿰援 寃곌낵뒗 YAP 諛쒖븫 寃쎈줈瑜 源껋쑝濡 븯뒗 븫뿉 븳 tankyrase inhibitor쓽 移섎즺 媛뒫꽦쓣 뮮諛쏆묠븳떎.

PTEN 以묒슂븳 醫낆뼇 뼲젣 씤옄씠硫 PTEN 룎뿰蹂씠뒗 뿬윭 븫(Li et al., 1997; Steck et al., 1997)怨 肄붾뜶利앺썑援(Liaw et al., 1997)怨 愿젴 엳떎. Tankyrase inhibition뿉 쓽븳 PTEN 븞젙솕뒗 AKT 씤궛솕쓽 븯뼢 議곗젅쓣 쑀룄븯뿬 꽭룷 利앹떇怨 醫낆뼇 꽦옣쓣 뼲젣븳떎(Li et al., 2015). 씠윭븳 뿰援 寃곌낵뒗 AKT 諛쒖븫 寃쎈줈瑜 源껋쑝濡 븯뒗 븫뿉 븳 tankyrase inhibitor쓽 移섎즺 媛뒫꽦쓣 뮮諛쏆묠븳떎.

Telomere: Telomere뒗 뿼깋泥 留먮떒뿉 쐞移섑븯뒗 蹂듯빀泥대줈 뿼깋泥 援ъ“쓽 븞젙꽦 쑀吏뿉 以묒슂븳 뿭븷쓣 븳떎(Blackburn et al., 1978). 꽭룷 遺꾩뿴 떆留덈떎 吏㏃븘吏뒗 telomere뒗 telomerase뿉 쓽븯뿬 빀꽦릺뒗뜲 씠윭븳 telomerase쓽 솢꽦 遺遺꾩쓽 븫꽭룷뱾뿉꽌 諛쒓껄릺뒗 듅吏뺤씠떎(Kim et al., 1994; Shay et al., 1997). Tankyrase 븫꽭룷뿉꽌 telomerase 빐瑜 議곗젅븯뿬 븫꽭룷쓽 吏냽쟻씤 利앹떇쓣 諛⑺빐븳떎(Smith et al., 2000; Chang et al., 2003). 씠윭븳 痢〓㈃뿉꽌 蹂 븣 telomerase쓽 솢꽦 뼲젣뒗 꽑깮쟻씤 븫 移섎즺瑜 쐞븳 깉濡쒖슫 諛⑸쾿 以묒쓽 븯굹濡 젣븞릺뿀떎. Tankyrase inhibitor telomerase inhibitor쓽 議고빀 쐞븫 諛 룓븫 꽭룷二쇱뿉꽌 긽듅맂 빆븫 슚怨쇰 蹂댁怨(Zhang et al., 2010; Ozaki et al., 2012), 룓븫 꽭룷쓽 옄硫몄쓣 珥됱쭊븯怨 꽭룷 利앹떇쓣 뼲젣븯뒗 寃껋쑝濡 굹궗떎(Lu et al., 2013). 씠윭븳 寃곌낵뒗 tankyrase inhibitor쓽 빆븫 슚怨 諛 tankyrase inhibitor telomerase inhibitor쓽 議고빀뿉 쓽븳 깉濡쒖슫 빆븫 移섎즺 媛뒫꽦쓣 뮮諛쏆묠븳떎.

쑀궗 遺꾩뿴: 쑀궗 遺꾩뿴 議곗젅젣: Tankyrase뒗 쑀궗 遺꾩뿴(mitosis) 떆 sister telomere cohesion 遺꾪빐, 以묒떖泥(centrosome) 떒諛깆쭏쓽 議곗젅뿉 愿뿬븳떎. Tankyrase inhibition 떆 쑀궗 遺꾩뿴 吏뿰怨 鍮꾩젙긽쟻씤 以묒떖泥 援ъ“ 諛 湲곕뒫 삤瑜 벑씠 諛쒖깮븳떎(Kim et al., 2012, 2014; Chang et al., 2005; Chang et al., 2005; Ozaki et al., 2012). 鍮꾩젙긽쟻씤 以묒떖泥대뒗 븫뿉 愿뿬븯怨 뿼깋泥 삤瑜(chromosome missegregation) 諛 씠닔 諛곗껜(aneuploidy)뿉 湲곗뿬븯뿬 븙꽦 吏꾪뻾쓣 珥됱쭊븳떎(Duensing et al., 2001; Boveri et al., 2008; Ganem et al., 2009; Guerrero et al., 2010). 씠 媛숈 寃곌낵瑜 諛뷀깢쑝濡 tankyrase inhibitor媛 쑀궗 遺꾩뿴 議곗젅젣濡 옉슜븯뿬 븫 移섎즺쓽 옞옱쟻 몴쟻쑝濡 媛뒫꽦씠 젣떆릺뿀떎(Korzeniewski et al., 2013).

Tankyrase inhibitor

留롮 뿰援щ 넻빐 븫 移섎즺젣濡쒖꽌쓽 tankyrase inhibitor쓽 以묒슂꽦怨 쑀슜꽦씠 蹂닿퀬릺뿀떎. 쁽옱源뚯 JW74, XAV939, AZ1366, IWR-1, G007-LK, JW55, NVP-TNKS656, WIKI4, Tetrazoloquinoxaline 41 (Waaler et al., 2012; Lau et al., 2013; Stratford et al., 2014; Tian et al., 2014; Bao et al., 2012; Scarborough et al., 2017; Quackenbush et al., 2016; Arqués et al., 2016; Thomson et al., 2017) 벑怨 媛숈 tankyrase inhibitor媛 蹂닿퀬릺뿀怨, 븫꽭룷 移섎즺뿉 슚怨쇰 蹂댁떎(Table 1). 몴쟻씤 XAV939, G007-LK, JW55뒗 β-catenin 븞젙꽦 몴쟻쑝濡 tankyrase瑜 빐븯뿬 AXIN쓣 븞젙솕븯怨 β-catenin 遺꾪빐瑜 珥됱쭊븳떎. 듅엳, APC 룎뿰蹂씠 옣븫 꽭룷뿉꽌 WNT 떊샇 쟾떖怨 醫낆뼇 꽦옣쓣 뼲젣븯뒗 tankyrase inhibition쓽 솗떎븳 슚怨쇨 엯利앸맖뿉 뵲씪 씠瑜 諛뷀깢쑝濡 븳 tankyrase inhibitor媛 諛쒕떖븯떎(Huang et al., 2009; Waaler et al., 2012; Lau et al., 2013). 援ъ껜쟻쑝濡 XAV939 G007-LK뒗 APC 룎뿰蹂씠 옣븫쓽 醫낆뼇 꽦옣쓣 뼲젣븳떎뒗 寃껋쓣 蹂댁뿬二쇱뿀떎(Wu et al., 2016). 삉븳, tankyrase inhibition쓣 넻븳 WNT 떊샇 쟾떖 寃쎈줈쓽 湲명빆 옉슜 룓븫 꽭룷뿉룄 슚怨쇱쟻씤 寃껋쑝濡 蹂닿퀬릺뿀怨(Casás-Selves et al., 2012; Busch et al., 2013), 떎젣濡 tankyrase inhibitor NVP-TNKS656씠 룓븫 꽭룷뿉 슚怨쇱쟻엫쓣 蹂댁뿬 以떎(Wang et al., 2016). 理쒓렐 깉濡쒖슫 tankyrase inhibitor씤 tetrazoloquinoxaline 41씠 뿬윭 醫낅쪟쓽 븫꽭룷뿉꽌 꽭룷二쇱쓽 꽦옣쓣 뼲젣븯뒗 슚怨쇰 蹂댁뿬 옞옱쟻씤 源껋쑝濡쒖쓽 媛뒫꽦씠 蹂닿퀬릺뿀떎(Thomson et al., 2017). Tankyrase inhibitor 떒룆쑝濡쒖쓽 븫꽭룷 빐 슚怨 肉먮쭔 븘땲씪 떎瑜 inhibitor뱾怨쇱쓽 蹂묓빀뿉 씤븳 빆븫 슚怨(Zhang et al., 2010; Ozaki et al., 2012; Lu et al., 2013)룄 蹂닿퀬맂 諛 깉濡쒖슫 빆븫 移섎즺 媛뒫꽦 諛 移섎즺 쟾왂씠 젣떆맆 寃껋쑝濡 삁긽맂떎.

Tankyrase inhibitors as therapeutic targets for cancer

 Tankyrase inhibitors Cancers References
JW 74OsteosarcomaStratford et al., 2014

XAV939NeuroblastomaTian et al., 2014
Colorectal cancer (CRC)Huang et al., 2009
Lung cancerBusch et al., 2013
Breast cancerBao et al., 2012

AZ1366Non-small cell lung cancer (NSCLC)Scarborough et al., 2017
Colorectal cancer (CRC)Quackenbush et al., 2016

IWR-1Lung cancerBusch et al., 2013
OsteosarcomaMartins-Neves et al., 2018

G007-LKColorectal cancer (CRC)Lau et al., 2013

JW55Colorectal cancer (CRC)Waaler et al., 2012

NVP-TNKS656Colorectal cancer (CRC)Arqués et al., 2016
Non-small cell lung cancer (NSCLC)Wang et al., 2016

WIKI4MelanomaJames et al., 2012

Tetrazoloquinoxaline 41Diverse cancer cell linesThomson et al., 2012

寃곕줎

Tankyrase뒗 떎뼇븳 꽭룷 湲곕뒫뿉 愿뿬릺뼱 엳쑝硫 以묒슂븳 븫 移섎즺 몴쟻씠떎. Tankyrase 떒諛깆쭏 AXIN, PTEN 諛 AMOT 媛숈 醫낆뼇 뼲젣 씤옄瑜 議곗젅븯怨 븫쓽 諛쒕퀝 썝씤씤 telomere 쑀吏 諛 쑀궗 遺꾩뿴 議곗젅뿉 愿뿬븳떎. Tankyrase inhibitor뒗 WNT, AKT 諛 YAP瑜 鍮꾨’븳 떎뼇븳 諛쒖븫 寃쎈줈瑜 몴쟻쑝濡 븯湲 븣臾몄뿉 tankyrase媛 븫 移섎즺쓽 슚怨쇱쟻씤 몴쟻씠 맆 닔 엳떎. 留롮 뿰援щ 넻빐 븫 移섎즺젣濡쒖꽌쓽 tankyrase inhibitor쓽 以묒슂꽦怨 쑀슜꽦씠 蹂닿퀬릺뿀떎. 듅엳, tankyrase inhibition뒗 APC 룎뿰蹂씠 寃곗옣 吏곸옣 븫꽭룷뿉꽌 WNT 떊샇 쟾떖 寃쎈줈 醫낆뼇 꽦옣쓣 뼲젣븯뒗 솗떎븳 슚怨쇨 엯利앸맖뿉 뵲씪 씠瑜 諛뷀깢쑝濡 븳 tankyrase inhibitor媛 諛쒕떖븯떎. 삁瑜 뱾뼱, XAV939 G007-LK뒗 APC 룎뿰蹂씠 옣븫 꽭룷쓽 醫낆뼇 꽦옣 뼲젣 슚怨쇰 솗떎엳 蹂댁뿬二쇱뿀떎. 뵲씪꽌 tankyrase inhibitor媛 븵쑝濡 APC 룎뿰蹂씠 옣븫뿉꽌 꽑깮쟻씤 빆븫 移섎즺젣 媛쒕컻뿉 以묒슂븯떎怨 궗猷뚮맂떎. 삉븳, tankyrase inhibitor씤 P-TNKS656씠 룓븫 꽭룷뿉 슚怨쇱쟻씠怨 깉濡쒖슫 tankyrase inhibitor씤 tetrazoloquinoxaline 41씠 뿬윭 醫낅쪟쓽 븫꽭룷뿉꽌 꽭룷二쇱쓽 꽦옣쓣 뼲젣븯뒗 슚怨쇨 蹂닿퀬맂 諛 tankyrase inhibitor媛 옣븫 쇅뿉룄 떎瑜 븫뿉꽌룄 슚怨쇨 엳쓣 寃껋쑝濡 삁긽맂떎. Tankyrase 떒諛깆쭏쓽 깉濡쒖슫 源껉낵 硫붿빱땲利섏뿉 愿젴맂 寃곌낵뱾씠 蹂닿퀬릺怨 엳뒗 諛 씠瑜 諛뷀깢쑝濡 븵쑝濡 떎뼇븳 븫뿉 븳 뜑 諛쒖쟾릺怨 吏꾪솕맂 tankyrase inhibitor媛 媛쒕컻릺怨 깉濡쒖슫 移섎즺 쟾왂씠 젣떆맆 寃껋쑝濡 삁긽맂떎.

ACKNOWLEDGEMENTS

This research was supported by the National Research Foundation of Korea (NRF-2015R1C1A1A02037631 to K.M.K.).

CONFLICT OF INTEREST

The author declares no conflict of interest.

References
  1. Arqu챕s O, Chicote I, Puig I, Tenbaum SP, Argil챕s G, Dienstmann R, Fern찼ndez N, Carat첫 G, Matito J, Silberschmidt D, Rodon J, Landolfi S, Prat A, Esp챠n E, Charco R, Nuciforo P, Vivancos A, Shao W, Tabernero J, and Palmer HG. Tankyrase Inhibition Blocks Wnt/棺-Catenin Pathway and Reverts Resistance to PI3K and AKT Inhibitors in the Treatment of Colorectal Cancer. Clinical Cancer Research 2016;22:644-656.
    Pubmed CrossRef
  2. Bao R, Christova T, Song S, Angers S, Yan X, and Attisano L. Inhibition of tankyrases induces Axin stabilization and blocks Wnt signaling in breast cancer cells. PloS One 2012;7:e48670.
  3. Beneke S, and B체rkle A. Poly (ADP-ribosyl) ation in mammalian ageing. Nucleic Acids Research 2007;35:7456-7465.
    Pubmed KoreaMed CrossRef
  4. Blackburn EH, and Gall JG. A tandemly repeated sequence at the termini of the extra chromosomal ribosomal RNA genes in Tetrahymena. Journal of Molecular Biology 1978;120:33-53.
    CrossRef
  5. Boveri T. Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. Journal of Cell Science 2008;121:1-84.
    Pubmed CrossRef
  6. B체rkle A. Poly (ADP-ribose). The most elaborate metabolite of NAD+. FEBS Journal 2005;272:4576-4589.
    Pubmed CrossRef
  7. Busch AM, Johnson KC, Stan RV, Sanglikar A, Ahmed Y, Dmitrovsky E, and Freemantle SJ. Evidence for tankyrases as antineoplastic targets in lung cancer. BMC Cancer 2013;13:211.
    Pubmed KoreaMed CrossRef
  8. Cas찼s-Selves M, Kim J, Zhang Z, Helfrich BA, Gao D, Porter CC, Scarborough HA, Bunn PA, Chan DC, Tan AC, and DeGregori J. Tankyrase and the canonical Wnt pathway protect lung cancer cells from EGFR inhibition. Cancer Research 2012;72:4154-4164.
    Pubmed KoreaMed CrossRef
  9. C.G.A. Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487:330-337.
    Pubmed KoreaMed CrossRef
  10. Chang P, Coughlin M, and Mitchison TJ. Tankyrase-1 polymerization of poly (ADP-ribose) is required for spindle structure and function. Nature Cell Biology 2005;7:1133-1139.
    Pubmed CrossRef
  11. Chang W, Dynek JN, and Smith S. TRF1 is degraded by ubiquitinmediated proteolysis after release from telomeres. Genes & Development 2003;17:1328-1333.
    Pubmed KoreaMed CrossRef
  12. Chang W, Dynek JN, and Smith S. NuMA is a major acceptor of poly (ADPribosyl) ation by tankyrase 1 in mitosis. Biochemical Journal 2005;391:177-184.
    Pubmed KoreaMed CrossRef
  13. Clevers H. Wnt/ 棺-catenin signaling in development and disease. Cell 2006;127:469-480.
    Pubmed CrossRef
  14. Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, Gayyed MF, Anders RA, Maitra A, and Pan D. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 2007;130:1120-1133.
    Pubmed KoreaMed CrossRef
  15. Duensing S, and Munger K. Centrosome abnormalities, genomic instability and carcinogenic progression. Biochimica et Biophysica Acta 2001;2:81-88.
  16. Ganem NJ, Godinho SA, and Pellma D. A mechanism linking extra centrosomes to chromosomal instability. Nature 2009;460:278-282.
    Pubmed KoreaMed CrossRef
  17. Guerrero AA, Martinez AC, and van Wely KH. Merotelic attachments and non-homologous end joining are the basis of chromosomal instability. Cell Division 2010;5:13.
    Pubmed KoreaMed CrossRef
  18. Guettler S, LaRose J, Petsalaki E, Gish G, Scotter A, Pawson T, Rottapel R, and Sicheri F. Structural basis and sequence rules for substrate recognition by tankyrase explain the basis for cherubism disease. Cell 2011;147:1340-1354.
    Pubmed CrossRef
  19. Guo HL, Zhang C, Liu Q, Li Q, Lian G, Wu D, Li X, Zhang W, Shen Y, Ye Z, Lin SY, and Lin SC. The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation. Cell Research 2012;22:1246-1257.
    Pubmed KoreaMed CrossRef
  20. Ha GH, Kim HS, Go H, Lee H, Seimiya H, Chung DH, and Lee CW. Tankyrase-1 function at telomeres and during mitosis is regulated by Polo-like kinase-1-mediated phosphorylation. Cell death and Differentiation 2012;19:321-332.
    Pubmed KoreaMed CrossRef
  21. Haikarainen T, Krauss S, and Lehtio L. Tankyrases:structure, function and therapeutic implications in cancer. Current Pharmaceutical Design 2014;20:6472-6488.
    Pubmed KoreaMed CrossRef
  22. Harvey KF, Zhang X, and Thomas DM. The Hippo pathway and human cancer. Nature Reviews Cancer 2013;13:246-257.
    Pubmed CrossRef
  23. Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, and Cong F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 2009;461:614-620.
    Pubmed CrossRef
  24. Kim MK, Dudognon C, and Smith S. Tankyrase 1 regulates centrosome function by controlling CPAP stability. EMBO Reports 2012;13:724-732.
    Pubmed KoreaMed CrossRef
  25. Kim MK, and Smith S. Persistent telomere cohesion triggers a prolonged anaphase. Molecular Biology of the Cell 2014;25:30-40.
    Pubmed KoreaMed CrossRef
  26. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, and Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science 1994;266:2011-2015.
    Pubmed CrossRef
  27. Korzeniewski N, Hohenfellner M, and Duensing S. The centrosome as potential target for cancer therapy and prevention. Expert Opinion on Therapeutic Targets 2013;17:43-52.
    Pubmed CrossRef
  28. Kraus W, and Lis JT. PARP goes transcription. Cell 2003;113:677-683.
    CrossRef
  29. Lau T, Chan E, Callow M, Waaler J, Boggs J, Blake RA, Magnuson S, Sambrone A, Schutten M, Firestein R, Machon O, Korinek V, Choo E, Diaz D, Merchant M, Polakis P, Holsworth DD, Krauss S, and Costa M. A novel tankyrase small-moleculeinhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Research 2013;73:3132-3144.
    Pubmed CrossRef
  30. Levaot N, Voytyuk O, Dimitriou I, Sircoulomb F, Chandrakumar A, Deckert M, Krzyzanowski PM, Scotter A, Gu S, Janmohamed S, Cong F, Simoncic PD, Ueki Y, La Rose J, and Rottapel R. Loss of tankyrase-mediated destruction of 3BP2 is the underlying pathogenic mechanism of cherubism. Cell 2011;147:1324-1339.
    Pubmed KoreaMed CrossRef
  31. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, and Parsons R. PTEN, a putative protein tyrosine phosphatase genemutated in human brain, breast, and prostate cancer. Science 1997;275:1943-1947.
    Pubmed CrossRef
  32. Li N, Zhang Y, Han X, Liang K, Wang J, Feng L, Wang W, Songyang Z, Lin C, Yang L, Yu Y, and Chen J. Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth. Genes & Development 2015;29:157-170.
    Pubmed KoreaMed CrossRef
  33. Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C, and Parsons R. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nature Genetics 1997;16:64-67.
    Pubmed CrossRef
  34. Lin L, Sabnis AJ, Chan E, Olivas V, Cade L, Pazarentzos E, Asthana S, Neel D, Yan JJ, Lu X, Pham L, Wang MM, Karachaliou N, Cao MG, Manzano JL, Ramirez JL, Torres JM, Buttitta F, Rudin CM, Collisson EA, Algazi A, Robinson E, Osman I, Mu챰oz-Couselo E, Cortes J, Frederick DT, Cooper ZA, McMahon M, Marchetti A, Rosell R, Flaherty KT, Wargo JA, and Bivona TG. The Hippo effector YAP promotes resistance to RAF and MEK-targeted cancer therapies. Nature Genetics 2015;47:250-256.
    Pubmed KoreaMed CrossRef
  35. Lu H, Lei Z, Lu Z, Lu Q, Lu C, Chen W, Wang C, Tang Q, and Kong Q. Silencing tankyrase and telomerase promotes A549 human lung adenocarcinoma cell apoptosis and inhibits proliferation. Oncology Reports 2013;30:1745-1752.
    Pubmed CrossRef
  36. Luo X, and Kraus WL. On PAR with PARP:cellular stress signaling through poly (ADP-ribose) and PARP-1. Genes & Development 2012;26:417-432.
    Pubmed KoreaMed CrossRef
  37. Malanga M, and Althaus FR. The role of poly (ADP-ribose) in the DNA damage signaling network. Biochemistry and Cell Biology 2005;83:354-364.
    Pubmed CrossRef
  38. Mo JS, Park HW, and Guan KL. The Hippo signaling pathway in stem cell biology and cancer. EMBO Reports 2014;15:642-656.
    CrossRef
  39. Nguyen DX, Chiang AC, Zhang XH, Kim JY, Kris MG, Ladanyi M, Gerald WL, and Massagu챕 J. WNT/TCF Signaling through LEF1 and HOXB9 Mediates Lung Adenocarcinoma Metastasis. Cell 2009;138:51-62.
    Pubmed KoreaMed CrossRef
  40. Ozaki Y, Matsui H, Asou H, Nagamach A, Aki D, Honda H, Yasunaga S, Takihara Y, Yamamoto T, Izumi S, Ohsugi M, and Inaba T. Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation. Molecular Cell 2012;47:694-706.
    Pubmed CrossRef
  41. Pacheco-Pinedo EC, Durham AC, Stewart KM, Goss AM, Lu MM, Demayo FJ, and Morrisey EE. Wnt/棺-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium. Journal of Clinical Investigation 2011;121:1935-1945.
    Pubmed KoreaMed CrossRef
  42. Quackenbush KS, Bagby S, Tai WM, Messersmith WA, Schreiber A, Greene J, Kim J, Wang G, Purkey A, Pitts TM, Nguyen A, Gao D, Blatchford P, Capasso A, Schuller AG, Eckhardt SG, and Arcaroli JJ. The novel tankyrase inhibitor (AZ1366) enhances irinotecan activity in tumors that exhibit elevated tankyrase and irinotecan resistance. Oncotarget 2016;7:28273-28285.
    Pubmed KoreaMed CrossRef
  43. Riffell JL, Lord CJ, and Ashworth A. Tankyrase-targeted therapeutics:expanding opportunities in the PARP family. Nature Reviews Drug Discovery 2012;11:923-936.
    Pubmed CrossRef
  44. Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, and Polakis P. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 1996;272:1023-1026.
    Pubmed CrossRef
  45. Scarborough HA, Helfrich BA, Cas찼s-Selves M, Schuller AG, Grosskurth SE, Kim J, Tan AC, Chan DC, Zhang Z, Zaberezhnyy V, Bunn PA, and DeGregori J. AZ1366:An Inhibitor of Tankyrase and the Canonical Wnt Pathway that Limits the Persistence of Non-Small Cell Lung Cancer Cells Following EGFR Inhibition. Clinical Cancer Research 2017;23:1531-1541.
    Pubmed KoreaMed CrossRef
  46. Shay JW, and Bacchetti S. A survey of telomerase activity in human cancer. European Journal of Cancer 1997;33:787-791.
    CrossRef
  47. Smith S, and de Lange T. Tankyrase promotes telomere elongation in human cells. Current Biology 2000;10:1299-1302.
    CrossRef
  48. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, and Tavtigian SV. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nature Genetics 1997;15:356-362.
    Pubmed CrossRef
  49. Stratford EW, Daffinrud J, Munthe E, Castro R, Waaler J, Krauss S, and Myklebost O. The tankyrase-specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines. Cancer Medicine 2014;3:36-46.
    Pubmed KoreaMed CrossRef
  50. Thomson DW, Wagner AJ, Bantscheff M, Benson RE, Dittus L, Duempelfeld B, Drewes G, Krause J, Moore JT, Mueller K, Poeckel D, Rau C, Salzer E, Shewchuk L, Hopf C, Emery JG, and Muelbaier M. Discovery of a Highly Selective Tankyrase Inhibitor Displaying Growth Inhibition Effects against a Diverse Range of Tumor Derived Cell Lines. Journal of Medicinal Chemistry 2017;60:5455-5471.
    Pubmed CrossRef
  51. Tian X, Hou W, Bai S, Fan J, Tong H, and Xu H. XAV939 inhibits the stemness and migration of neuroblastoma cancer stem cells via repression of tankyrase 1. International Journal of Oncology 2014;45:121-128.
    Pubmed CrossRef
  52. Waaler J, Machon O, Tumova L, Dinh H, Korinek V, Wilson SR, Paulsen JE, Pedersen NM, Eide TJ, Machonova O, Gradl D, Voronkov A, von Kries JP, and Krauss S. A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice. Cancer Research 2012;72:2822-2832.
    Pubmed CrossRef
  53. Wang H, Lu B, Castillo J, Castillo J, Zhang Y, Yang Z, McAllister G, Lindeman A, Reece-Hoyes J, Tallarico J, Russ C, Hoffman G, Xu W, Schirle M, and Cong F. Tankyrase Inhibitor Sensitizes Lung Cancer Cells to Endothelial Growth Factor Receptor (EGFR) Inhibition via Stabilizing Angiomotins and Inhibiting YAP Signaling. Journal of Biological Chemistry 2016;291:15256-15266.
    Pubmed KoreaMed CrossRef
  54. Wang W, Huang J, and Chen J. Angiomotin-like proteins associate with and negatively regulate YAP. Journal of Biological Chemistry 2011;286:4364-4370.
    Pubmed KoreaMed CrossRef
  55. Wang W, Li N, Li X, Tran MK, Han X, and Chen J. Tankyrase inhibitors Target YAP by Stabilizing Angiomotin Family Proteins. Cell Reports 2015;13:524-532.
    Pubmed KoreaMed CrossRef
  56. Wu X, Luo F, Li J, Zhong X, and Liu K. Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway. International Journal of Oncology 2016;48:1333-1340.
    Pubmed KoreaMed CrossRef
  57. Yeh TY, Sbodio JI, Tsun ZY, Luo B, and Chi NW. Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase. Biochemical Journal 2007;402:279-290.
    Pubmed KoreaMed CrossRef
  58. Zhang H, Yang MH, Zhao JJ, Chen L, Yu ST, Tang XD, Fang DC, and Yang SM. Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors. Oncology Reports 2010;24:1059-1065.
    Pubmed