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1 연구분야 ( 코드 ) 과제번호 과제성격 ( 기초, 응용, 개발 ) 연구과제명 과제책임자 세부과제 실용화대상여부 실용화 / 비실용화 지원 ex) 창의 프로그램 ( 일반연구 ) 과제공개가능여부공개 ( 공개, 비공개 ) ( 국문 ) ( 영문 ) 구분 소 속 비교생명의학연 구과 직위 성명김용연전공분자세포생물학 세부과제명 세부과제책임자 성명 소속 ( 직위 ) 전공 총연구기간 참여연구원수 ( 단위 : 명, MY) 연구기간및 연구비 ( 단위 : 천원 ) 구분연구기간계 계 ~ 295,000 제 1 차 120,000 제 2 차 100,000 제 3 차 75,000 국립암센터 참여기업명칭전화 FAX 기업부담금소계현금현물 기관고유연구사업관리규칙에따라본연구개발사업을성실히수행하였으며아래와같이최종보고서 를제출합니다 년 10 월 30 일 과제책임자김용연 ( 서명 )

2 작성요령

4 연구목표 (200 자이내 ) 연구내용및방법 (500 자이내 ) < 최종목표 > α α 연구개발에따른기대성과

5 색인어 국문 영문 세포부착성상실세포사멸 표피성장인자수용체 EMT 암전이 녹스4 lipid raft 암전이쥐모델 Src anoikis EGFR EMT cancer metastasis Nox4 lipid raft metastasis mouse model Src

6 EGFR, Nox4, Src, anoikis, cancer metastasis, metastasis mouse model, EMT, lipid raft Yong-Nyun Kim

8 κ

9 δ δ δ β γ TGF-β, TrkB (Neurotropic tyrosine kinase receptor B) FGF EMT Twist, Snail, Zeb1 및 E-cadherin과같은 EMT의 key regulators가 EMT 과정동안 anoikis resistance를증가시킴. g g

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46 실험결과에대한종합적고찰 1. Nox4 발현조절과 anoikis 조절기전규명 : Nox4 의발현이 EGFR 에의해조절되며, EGFR 의 발현과활성또한 Nox4 에의해조절됨을확인하였으며, Nox4 나 EGFR 을 knock-down 했을때 anoikis 가증가함을확인함. 2. Skp2와 CDCP1의발현조절과 anoikis 조절기전규명 : 새로운 anoikis regulator로예상된 Skp2와 CDCP1의발현이 EGFR과 Her-2에의해조절됨을확인하였으며, 특히 CDCP1의경우 anoikis resistance 뿐만아니라 cell adhesion, anchorage-independent cell growth 에중요함을확인함. 3. 부착성에따른 energy metabolism 차이규명 : suspended cancer cell이 suspended normal cell보다세포내 ATP 양과 glucose uptake 양의감소가억제됨을확인함으로써, suspended cancer cell이 energy metabolism을조절하여 anoikis resistance을가지는것으로예상됨. 4. anoikis resistant cancer cell line 수립 : mouse bladder cancer cell line인 MBT-2 cell을 syngeneic mouse (C3H-HE mouse) 의 bladder에 injection 하여 kidney나 lung에전이된암조직을추출하여 primary culture하여세포주를만들고, 이렇게만들어진세포주를다시두번더반복하여단계적인 metastasis model cell line을구축함. 실험결과에대한종합적고찰

47 -, GFP, CTC

49 Anoikis Resistance: An Essential Prerequisite for TumorMetastasis 김용연 ( 제 1 저자, 교신 ) International Journal of Cell Biology ~ 국외 CK20 Expression Enhances the Invasiveness of Tamoxifen-resistant MCF-7 Cells Anticancer research (1.725, 2011) 2013; 32(4); 1221~1228 An In Vivo C. elegans Model System for Screening EGFR Inhibiting Anti-Cancer Drugs STAT3-RANTES autocrine signaling is essential for tamoxifen resistance in human breast cancer cells Lipid raft modulation by Rp1 reverses multidrug resistance via inactivating MDR-1 and Src inhibition Salinomycin induces cell death via inactivation of Stat3 and downregulation of Skp2 Simple and Versatile Molecular Method of Copy-Number Measurement Using Cloned Competitors Identification of annexin II as a novel secretory biomarker for breast cancer Down-regulation of lipid raft-associated onco-proteins via cholesterol-dependent lipid raft internalization in docosahexaenoic acid-induced apoptosis Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H-Ras-induced epithelial to mesenchymal transition Interferon consensus sequence-binding protein (ICSBP) promotes epithelial-to-mesenchymal transition (EMT)-like phenomena, cell-motility, and invasion via TGF-β signaling in U2OS cells. PLosOne (4.092, 2011) Molecular Cancer Research (4.353, 2012) Biochemical Pharmacology (4.576, 2012) Cell Death and Disease (6.044, 2012) PLos One (3.73, 2012) Proteomics (4.132, 2012) Biochimica et 2013; 7(9); e42441~e ; 11(1); 31~ ; 85(10);1441 ~ ; 4; e ; 69414~ ; 13; 3145~3156 BiophysicaActa- 2014; Molecular and Cell Biology of 1841(1): Lipids (4.495, 2013) Int J Cancer (5.007, 2013) Cell Death and Disease (5.177, 2013) 190~ ; doi: /ijc ; 5:e1224~e12 24

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56 EMBO molecular medicine (8.235, 2013)

57 [1] S. Li, S. S. Tabar, V. Malec, B. G. Eul, W. Klepetko, N. Weissmann, F. Grimminger, W. Seeger, F. Rose and J. Hanze, "NOX4 regulates ROS levels under normoxic and hypoxic conditions, triggers proliferation, and inhibits apoptosis in pulmonary artery adventitial fibroblasts," Antioxid Redox Signal, vol. 10, no. 10, pp , [2] E. Giannoni, F. Buricchi, G. Grimaldi, M. Parri, F. Cialdai, M. L. Taddei, G. Raugei, G. Ramponi and P. Chiarugi, "Redox regulation of anoikis: reactive oxygen species as essential mediators of cell survival," Cell Death Differ, vol. 15, no. 5, pp , [3] E. Giannoni, T. Fiaschi, G. Ramponi and P. Chiarugi, "Redox regulation of anoikis resistance of metastatic prostate cancer cells: key role for Src and EGFR-mediated pro-survival signals," Oncogene, vol. 28, no. 20, pp , [4] R. A. Cairns, I. S. Harris and T. W. Mak, "Regulation of cancer cell metabolism," Nat Rev Cancer, vol. 11, no. 2, pp , [5] Z. T. Schafer, A. R. Grassian, L. Song, Z. Jiang, Z. Gerhart-Hines, H. Y. Irie, S. Gao, P. Puigserver and J. S. Brugge, "Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment," Nature, vol. 461, no. 7260, pp , [6] R. Lock, S. Roy, C. M. Kenific, J. S. Su, E. Salas, S. M. Ronen and J. Debnath, "Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation," Mol Biol Cell, vol. 22, no. 2, pp , [7] M. L. Taddei, E. Giannoni, T. Fiaschi and P. Chiarugi, "Anoikis: an emerging hallmark in health and diseases," J Pathol, vol. no. pp [8] T. Uekita, L. Jia, M. Narisawa-Saito, J. Yokota, T. Kiyono and R. Sakai, "CUB domain-containing protein 1 is a novel regulator of anoikis resistance in lung adenocarcinoma," Mol Cell Biol, vol. 27, no. 21, pp , [9] S. M. Frisch and H. Francis, "Disruption of epithelial cell-matrix interactions induces apoptosis," J Cell Biol, vol. 124, no. 4, pp , [10] C. D. Simpson, K. Anyiwe and A. D. Schimmer, "Anoikis resistance and tumor metastasis," Cancer letters, vol. 272, no. 2, pp , [11] P. Chiarugi and E. Giannoni, "Anoikis: a necessary death program for anchorage-dependent cells," Biochem Pharmacol, vol. 76, no. 11, pp , [12] M. J. Reginato, K. R. Mills, J. K. Paulus, D. K. Lynch, D. C. Sgroi, J. Debnath, S. K. Muthuswamy and J. S. Brugge, "Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis," Nat Cell Biol, vol. 5, no. 8, pp , [13] T. T. Onder, P. B. Gupta, S. A. Mani, J. Yang, E. S. Lander and R. A. Weinberg, "Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways," Cancer research, vol. 68, no. 10, pp , 2008 [14] P. W. Derksen, X. Liu, F. Saridin, H. van der Gulden, J. Zevenhoven, B. Evers, J. R. van Beijnum, A. W. Griffioen, J. Vink, P. Krimpenfort, J. L. Peterse, R. D. Cardiff, A. Berns and J. Jonkers, "Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis," Cancer Cell, vol. 10, no. 5, pp , [15] J. Yang, S. A. Mani, J. L. Donaher, S. Ramaswamy, R. A. Itzykson, C. Come, P. Savagner, I. Gitelman, A. Richardson and R. A. Weinberg, "Twist, a master regulator of morphogenesis, plays

58 an essential role in tumor metastasis," Cell, vol. 117, no. 7, pp , [16] M. A. Smit and D. S. Peeper, "Zeb1 is required for TrkB-induced epithelial-mesenchymal transition, anoikis resistance and metastasis," Oncogene, vol. 30, no. 35, pp , [17] S. Kumar, S. H. Park, B. Cieply, J. Schupp, E. Killiam, F. Zhang, D. L. Rimm and S. M. Frisch, "A Pathway for the Control of Anoikis Sensitivity by E-Cadherin and Epithelial-to-Mesenchymal Transition," Mol Cell Biol, vol. 31, no. 19, pp , [18] A. R. Grassian, Z. T. Schafer and J. S. Brugge, "ErbB2 Stabilizes Epidermal Growth Factor Receptor (EGFR) Expression via Erk and Sprouty2 in Extracellular Matrix-detached Cells," Journal of Biological Chemistry, vol. 286, no. 1, pp. 79, [19] L. Wei, Y. Yang, X. Zhang and Q. Yu, "Altered regulation of Src upon cell detachment protects human lung adenocarcinoma cells from anoikis," Oncogene, vol. 23, no. 56, pp , [20] O. Warburg, "On the origin of cancer cells," Science, vol. 123, no. 3191, pp , [21] G. L. Semenza, P. H. Roth, H. M. Fang and G. L. Wang, "Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1," J Biol Chem, vol. 269, no. 38, pp , [22] J. W. Kim, I. Tchernyshyov, G. L. Semenza and C. V. Dang, "HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia," Cell Metab, vol. 3, no. 3, pp , [23] D. B. Shackelford and R. J. Shaw, "The LKB1-AMPK pathway: metabolism and growth control in tumour suppression," Nat Rev Cancer, vol. 9, no. 8, pp , [24] C. Fung, R. Lock, S. Gao, E. Salas and J. Debnath, "Induction of autophagy during extracellular matrix detachment promotes cell survival," Mol Biol Cell, vol. 19, no. 3, pp , [25] E. Gottlieb, "Cancer: The fat and the furious," Nature, vol. 461, no. 7260, pp , [26] R. Lock, S. Roy, C. M. Kenific, J. S. Su, E. Salas, S. M. Ronen and J. Debnath, "Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation," Mol Biol Cell, vol. 22, no. 2, pp , [27] E. Giannoni, T. Fiaschi, G. Ramponi and P. Chiarugi, "Redox regulation of anoikis resistance of metastatic prostate cancer cells: key role for Src and EGFR-mediated pro-survival signals," Oncogene, vol. 28, no. 20, pp , [28] P. Zhu, M. J. Tan, R. L. Huang, C. K. Tan, H. C. Chong, M. Pal, C. R. Lam, P. Boukamp, J. Y. Pan, S. H. Tan, S. Kersten, H. Y. Li, J. L. Ding and N. S. Tan, "Angiopoietin-like 4 protein elevates the prosurvival intracellular O2(-):H2O2 ratio and confers anoikis resistance to tumors," Cancer Cell, vol. 19, no. 3, pp , [29] M. C. Guadamillas, A. Cerezo and M. A. Del Pozo, "Overcoming anoikis - pathways to anchorage-independent growth in cancer," J Cell Sci, vol. 124, no. Pt 19, pp , [30] Y. C. Li, M. J. Park, S. K. Ye, C. W. Kim and Y. N. Kim, "Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents," Am J Pathol, vol. 168, no. 4, pp ; quiz , 2006.

작성요령

작성요령 지원연구분야 ( 코드 ) I-4 과제번호 1310740-1 모험프로그램공개가능여부과제성격 ( 기초, 응용, 개발 ) 응용실용화대상여부실용화비공개 ( 공개, 비공개 ) ( 국문 )IVIM (3차원화소내비간섭성운동영상 ) 을위한소프트웨어개발과유 연구과제명 과제책임자 세부과제 방암으로의임상적용을위한예비연구 ( 영문 )Development of software for