Download Syndecan-2 as an emerging target for migration

2009 Matrix Biology 연구회 심포지엄
일 시 : 2009 년 8 월 24 일(월) 13:30~18:00
장 소 : 경북대학교 의학전문대학원 중앙강당
주 관 : Matrix Biology 연구회
주 최 : 경북대학교 세포․기질연구소
1
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Program
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PART I
13:30-14:00
등록 및 개회
14:00-14:20
Syndecan-2 as an emerging target for migration-related
diseases
14:20-14:30
질의 및 응답
14:30-14:50
TM4SF5-mediated regulation of cell functions under
collagen type I
14:50-15:00
김인산교수
오억수교수
(이화여대)
이정원교수
(서울대)
질의 및 응답
15:00-15:20
Function of ABH blood group antigen in human skin
keratinocytes
15:30-15:40
질의 및 응답
오장희박사/
정진호교수
(서울대)
Coffee Break
15:40-16:10
PART II
16:10-16:30
Bi-modal regulation of Wnt signaling pathway by DP1
16:30-16:40
질의 및 응답
16:40-17:00
17:00-17:10
Concentration dependent dual effect of thrombin in
endothelial cells via PAR-1 and PI3 kinase
질의 및 응답
2
조익훈교수
(서울시립대)
배종섭교수
(대구한의대)
17:10-17:30
17:30-17:40
A New Mechanism of Rapid Clearance of Apoptotic
Cells
김인산교수
(경북대)
질의 및 응답
17:40-18:00
폐회 및 기념 촬영
김인산교수
Eok-soo Oh, Ph.D.
Address : Ewha Womans University
Department of Life Sciences
Daehyun-dong, Seodaemoon-Gu
Seoul 120-750 Korea
TEL : 02-3277-3791
E-mail : [email protected]
Experiences:
Harvard Medical School
1997.03 – 1999.02 Post-doctoral Research Scientist
Ewha Womans University
1999.03 – 2004.02 Assistant Professor
Ewha Womans University
2004.03 – 2009.02
Associate Professor
Burnham Institute for Medical Research 2007.02 – 2008.02
Visiting Scholar
Ewha Womans University
2009.03 – present
Professor
Publications:
Lee JH, Park H, Chung H, Choi S, Kim Y, Yoo H, Kim TY, Hann HJ, Seong I, Kim J, Kang KG,
Han IO, Oh ES. 2009. Syndecan-2 regulates the migratory potential of melanoma cells. J
Biol Chem. (in press)
Kwon S, Son H, Choi Y, Lee JH, Choi S, Lim Y, Han IO, Oh ES. 2009. Syndecan-4 promotes
the retention of phosphatidylinositol 4,5-bisphosphate in the plasma membrane. FEBS
Lett. 583:2395-2400.
Choi S, Kim Y, Park H, Han IO, Chung E, Lee SY, Kim YB, Lee JW, Oh ES, Yi JY. 2009.
Syndecan-2 overexpression regulates adhesion and migration through cooperation with
integrin alpha2. Biochem Biophys Res Commun. 384:231-235
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Oh MA, Choi S, Lee MJ, Choi MC, Lee SA, Ko W, Cance WG, Oh ES, Buday L, Kim SH, Lee
JW. 2009. Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer
tyrosine kinase in suspended hepatocytes. Biochim Biophys Acta. 1793:781-791.
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Syndecan-2 as an emerging target for migration-related diseases
Eok-Soo Oh
Department of Life Sciences, Division of Molecular Life Sciences, Ewha Womans University Seoul
Korea
The syndecans, a major family of transmembrane cell surface heparan sulfate proteoglycans,
regulate ECM-mediated signal transduction including cell adhesion and migration. While syndecan-1
and syndecan-4 are known to inhibit cell migration, several reports indicate that syndecan-2 may
have the opposite effect as the gene is highly expressed in cells under migratory conditions.
Consistently, the expression of syndecan-1 and –4 is decreased in several cancer cell lines, while that
of syndecan-2 was increased in colon cancer, melanoma and fibrosarcoma cells, consistent with their
migratory characteristics. The expression of syndecan-2 was elevated in tissue samples from malignant
human cancer tissues and was critical for adhesion and proliferation as well as other tumorigenic
behaviors including increased metastasis of those cancer cell lines. Therefore, increased syndecan-2
expression appears to play a crucial role as a receptor for cancer cell migration. However, the
underlying molecular mechanism is still unclear. At the first part, current state of knowledge of the
molecular regulatory mechanism of syndecan-2-mediated migration in several cancer cells will be
presented. Recent advances in cell migration research have provided new insights into how
aberrations in migration impact human diseases, including vascular disease, chronic inflammatory
diseases, tumor formation and metastasis. Therefore, at the later part, it will be presented the
possibility of the involvement of syndecan-2 in human diseases and syndecan-2 as a new target for
migration-related diseases.
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Lee, Jung Weon
: Feb. 6th, 1963
: Korea (Republic of)
E-mail; [email protected]
(Lab) 82-2-3668-7030, 7421, 7472 (Fax) 82-2-766-4487
Mailing address; Associate Professor
Cancer Research Institute, College of Medicine
Seoul National University
103, Daehangno, Jongno-Gu, Seoul, 110-799 Korea
Date of birth
Nationality
Address:
PROFESSIONAL EXPERIENCE
2001.11~now
2001 ~ 2001.10
1995 ~ 1996
1993 ~ 1995
1990 ~ 1992
Assistant/Associate Professor
Department of Tumor Biology
Department of Molecular and Clinical Oncology
Cancer Research Institute, College of Medicine
Seoul National University, Seoul, Korea
Seoul, Korea
Research Fellow
Memorial Sloan-Kettering Cancer Center
New York, USA
Research Technician II,
Department of Pharmacology
University of North Carolina
Chapel Hill, NC, USA
Teaching assistant, Biochemistry Lab
Department of Biochemistry
University of Tennessee
Knoxville, TN, USA
Researcher
Department of Plant Biochemistry
Rural Development Institute
Suwon, Korea
PUBLICATIONS
1. S-A Lee, Y.M Kim, S Choi, M Lee, T-G Gwak, H.J. Kim, S Kim, S-H Kim, K H Park, HJ Kim, M. Cho,
and J. W. Lee (corresponding author) (2009) The extracellular loop 2 of TM4SF5 inhibits integrin
α2 on hepatocytes under collagen type I environment. (In Revision).
2. S-A Lee, S Choi, M Lee, T-G Gwak, H.J. Kim, S Kim, S-H Kim, K H Park, HJ Kim, M. Cho, and J. W.
Lee (corresponding author) (2009) Four-transmembrane L6 family member 5 (TM4SF5)
enhances migration and invasion of hepatocytes for effective metastasis (Submitted)
3. S Choi, Y Kim, H Park, IO Han, E Chung, SY Lee, YB Kim, JW Lee, ES Oh, and JY Yi (2009)
Syndecan-2 overexpression regulates adhesion and migration through cooperation with integrin
Biochem Biophys Res Commun. 384(2) 231-235.
4. E-K Park, M J Park, S-H Lee, Y C Li, J Kim, J-S Lee, J.W. Lee, S-K Ye, J-W Park, C-W Kim, B-K
Park, and Y-N Kim. (2009) Cholesterol depletion induces anoikis-like apoptosis via FAK downregulation and caveolae internalization. Journal of Pathology. 218(3) 337-349.
5. M-A Oh, S Choi, M Lee, S-A Lee, WG. Cance, E-S Oh, L Buday, S-H Kim, and J. W. Lee
(corresponding author). (2009) Specific tyrosine phosphorylation of Focal Adhesion Kinase by Fer
tyrosine kinase in suspended hepatocytes. BBA-Mol. Cell Res. 1793(5) 781-791.
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TM4SF5-mediated regulation of cell functions under collagen type I
Sin-Ae Lee and JUNG WEON LEE.
Seoul National University, Seoul Korea
Four-transmembrane L6 family member 5 (TM4SF5) and its homologue L6, a tumor antigen, form a
four-transmembrane L6 family. TM4SF5 expression causes uncontrolled cell proliferation and
angiogenesis. Although other genuine transmembrane 4 superfamily (TM4SF) members cooperate
with integrins for cell migration, roles of TM4SF5 in the cellular spreading and migration are
unknown. Using hepatocarcinoma cell clones that ectopically express TM4SF5, we found that crosstalks via an interaction between TM4SF5 and
-environment inhibited
using a peptide or mutagenesis.
regula
2009.09 ~
2001.11 ~ 2009.08
2001.01 ~ 2001.10
NY, USA
1996.08 ~ 2000.12
1992.08 ~ 1995.08
1986.03 ~ 1998.02
1982.03 ~ 1986.02
Altogether, the observations suggest that TM4SF5 negatively
Associate Professor,
College of Pharmacy, SNU
Assistant/Associate Professor
College of Medicine, SNU
Research Fellow
Memorial Sloan-Kettering Cancer Center,
Ph.D.
MS
MS
BS
U. of North Carolina @ Chapel Hill, NC, USA
U. of Tennessee @ Knoxville, TN, USA
Seoul National University
Seoul National University
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JIN HO CHUNG, M.D., Ph.D.
AFFILIATION
Professor
Department of Dermatology
Seoul National University Hospital
28 Yongon-dong, Chongro-gu, Seoul 110-744, Korea
Tel: 82-2-2072-2414
E-mail: [email protected]
PROFESSIONAL EXPERIENCE
1984.03-1985.02 Internship, Seoul National University Hospital, Seoul, Korea
1985.03-1988.02 Resident, Department of Dermatology, Seoul National University
Hospital, Seoul, Korea
1988.03-1991.04 A staff doctor, Department of Dermatology, Capital Armed Forces
General Hospital, Seoul, Korea
1991.05-1993.02 Research Fellowship, Department of Dermatology, Seoul National
University College of Medicine, Seoul, Korea
1997.03-1999.02 Research Fellow, Department of Dermatology, University of
Michigan, USA
1993.03- Present Instructor, Assistant Prof., Research Fellow, Associate Prof.,
Professor, Department of Dermatology, Seoul National University
College of Medicine, Seoul, Korea
2007.11-Present Fellow, Medical Sciences Division, The Korean Academy of Science
and Technology, Seoul, Korea
AWARD
1992, 1995, 2001 - Donga Academic prize in The Korean Dermatological Association
2003 - Young Investigator’s prize in Seoul National University Hospital
2003 - In-Bong Academic prize in The Korean Dermatological Association
2003 - A Special jury prize for Reserch paper in European Academy Dermatology &
Venereology
2005 – SCI I.F prize in Seoul National University Hospital, Seoul National University College of
Medicine Dean
8
Function of ABH blood group antigen in human skin keratinocytes
Jang-Hee Oh, Ji Young Jung, Jin Ho Chung
Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous
Aging Research, Clinical Research Institute, Seoul National University Hospital, Institute of
Dermatological Science, Seoul National University, Seoul, Korea
Since ABH blood group antigen was found on the surface of red blood cells in 1900, many tissues of
human body have been demonstrated to express ABH blood group antigen and their precursors,
including skin. In vivo, human skin tissue expresses ABH antigens only in fully differentiated
epidermal keratinocytes, called the granular layer. H antigen is the precursor for A or B antigen,
synthesized by addition of N-D-acetylgalactosamine or D-galactose to H antigen, respectively. This
reaction is mediated by the specific glycosylating enzymes, coded by the individual’s polymorphism of
ABO gene, and if the gene products have no activity, that individual should have O blood type. The
synthesis of H antigen is generally mediated by fucosyltransferase 1 (FUT1) or fucosyltransferase 2
(FUT2), responsible for type 2 H antigen or type 1 H antigen, respectively. Type 2 H antigen is known
as the major form in human skin, but type 1 H antigen is not detected. Therefore, we examined the
expression of ABH blood group antigen in many pathological conditions. Decrease of ABH antigen
expression was demonstrated in many skin inflammatory diseases, including atopic dermatitis,
psoriasis, and contact dermatitis. Decrease of ABH antigen expression was also demonstrated in
ultraviolet irradiated buttock skin. To investigate the function of ABH antigens in skin keratinocytes,
siRNAs of ABO and FUT1 genes were transfected into HaCaT keratinocyte cell lines, and the changes
of FBS-induced cell motility and IFNγ-induced ICAM-1 expression were examined. The ABO and
FUT1 siRNA-transfected HaCaT cells showed less closure rates in the scratch assay than negative
control scrambled siRNA transfected HaCaT cells. The FUT1 siRNA-transfected HaCaT cells showed
less IFNγ-induced ICAM-1 expression than ABO and negative control scrambled siRNA transfected
HaCaT cells. In conclusion, ABH blood group antigens in human skin may have physiological
functions and involvement in skin inflammatory responses.
9
Eek-hoon Jho, Ph.D.
Address : The University of Seoul
Department of Life Science
90 Jeonnong-dong, Dongdaemun-gu
Seoul, 130-743, Korea
TEL : 02-2210-2681
E-mail : [email protected]
Birth date: 11 April 1963
Experiences:
Michigan State University
SUNY at Stony Brook
1990.9 - 1995.10
1995.11 - 1997.2
Teaching Assistant
Post-doctoral Research Scientist
Columbia University (New York)
The University of Seoul
University of Southern California
The University of Seoul
1997.3 - 2000.12
2001.9 – 2005.9
2007.12-2008.12
2005.10 –present
Associate Research Scientist
Assistant Professor
Visiting Scholar
Associate Professor
Publications:
Jung H, Kim HJ, Lee SK, Kim R, Kopachik W, Han JK, Jho EH. 2009. Negative feedback
regulation of Wnt signaling by Gbg-mediated reduction of Dishevelled. Exp Mol Med. In press.
Kim JA, Kang YJ, Park G, Kim M, Park YO, Kim H, Lee SH, Chu IS, Lee JS, Jho EH and Oh IH.
2009. Identification of a stroma-mediated Wnt/-catenin signal promoting self-renewal of
hematopoietic stem cells in stem cell niche. Stem Cells. 27(6):1318-29.
Kim H, Cheong SM, Ryu J, Jung HJ, Jho EH and Han JK. 2009. Xenopus Wntless and the
Retromer complex cooperate to regulate XWnt4 secretion. Mol Cell Biol. 29(8):2118-28.
Kim SM, Choi E, Song, K, Kim S, Seo E, Jho EH, Kee SH. 2009. Axin localizes to mitotic
spindles and centrosomes in mitotic cells. Exp Cell Res. 315(6):943-54.
Seo E, Kim S, Jho EH. 2009. Induction of cancer cell-specific death via MMP2 promoterdependent expression of Bax. BMB reports. 42(4):217-22.
10
Bi-modal regulation of Wnt signaling pathway by DP1
Wantae Kim1, Hyunjoon Kim2, Minhye Kim1, Jin-Kwan Han2 and Eek-hoon Jho1
Department of Life science, University of Seoul, Seoul, Korea, 130-743, 2Division of Molecular and
Life sciences, Pohang University of Science and Technology, Kyungbuk, Korea, 790-784
1
Dimerization Partner 1 (DP1) is known to enhance cellular activity of E2F by dimerization with E2F.
The data from genome-wide screening of siRNA using Drosophila cell line suggested that DP1
-catenin signaling, while the underlying molecular mechanism was not
known. Here, we provide molecular mechanisms for DP1 in the regulation of Wnt signaling in
mammalian cells. DP1 enhances Wnt3a mediated reporter activity while it blocks the reporter
-catenin. Consistent with these effects in HEK293T cells, injection
of DP1 into Xenopus embryos enhanced the formation of secondary axes induced by XWnt8, but
interacts with Dvl and Axin in vivo. The interaction between Axin and Dvl is severely blocked in the
presence of DP1.
-catenin via
induction of poly-ubiquitination, which may explain how DP1 inhibits the reporter activity induced
-catenin. Interestingly, Wnt signaling increases the nuclear localization of DP1 and it
-catenin mediated Tcf activation and the binding of NLK
with DP1 seems to relieve the antagonistic activity of NLK. It may be a possible explanation for how
DP1 enhances Wnt mediated reporter activity. Overall our results suggest that DP1 in the different
cellular localization may have opposite roles in the regulation of Wnt signaling.
(This work is supported by the grants from KOSEF and Brain Korea 21 program.)
11
Jong-Sup Bae, Ph.D.
AFFILIATION
Assistant Professor
Department of Herbal Pharmaceutical Engineering
Daegu Haany University
290 Yugok-dong, Gyeongsan-si, Gyeongsangbuk-do, Korea
Tel: 82-53-819-1498
E-mail: [email protected]
PROFESSIONAL EXPERIENCE
2002. 7 – 2003. 8: Research Associate, School of Medicine, Kyungpook National
University, Korea
2008. 6 – 2008. 8: Research Associate (Post-Doc), Department of Biochemistry and Molecular
Biology, St. Louis University School of Medicine
2008. 9 : Assistant Professor, Department of Herbal
Pharmaceutical Engineering, Daegu Haany University.
AWARD
2001. 10: Best Poster Award in 2001, Korean Society of Medical Biochemistry and Molecular
Biology
2006. 12: Travel Award in the 48th Annual Meeting of Hematology
2007. 02: 한국을 빛낸 사람들 등록 (with PNAS Paper)
2007. 09: 한국을 빛낸 사람들 등록 (with Blood Paper)
2007. 12: Travel Award in the 49th Annual Meeting of Hematology
SEPCIALITY AND RESEARCH FIELD OF INTEREST
Cellular signaling related to blood coagulation cascade
Inflammation related diseases
Development herbal medicine for inflammatory responses
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Concentration dependent dual effect of thrombin in endothelial
cells via PAR-1 and PI3 kinase
배 종 섭, 대구한의대학교
Disruption of endothelial barrier is a critical pathophysiological factor in inflammation. Thrombin
exerts a variety of cellular effects including inflammation and apoptosis through activation of the
protease activated receptors (PARs). The activation of PAR-1 by thrombin is known to have a
bimodal effect in endothelial cell permeability with a low concentration (pM levels) eliciting a barrier
protective and a high concentration (nM levels) eliciting a barrier disruptive response. It is not known
whether this PAR-1-dependent activity of thrombin is a unique phenomenon specific for the in vitro
assay or it is part of a general anti-inflammatory effect of low concentrations of thrombin that may
have a physiological relevance. Here, we report that low concentrations of thrombin or of PAR-1
agonist peptide induced significant anti-inflammatory activities. However, relatively high
concentration of thrombin or of PAR-1 agonist peptide showed pro-inflammatory activities. By using
function-blocking anti-PAR-1 antibodies and PI3 kinase inhibitor, we show that the direct antiinflammatory effects of low concentrations of thrombin are dependent on the activation of PAR-1
and PI3 kinase. These results suggest a role for cross communication between PAR-1 activation and
PI3 kinase pathway in mediating the cytoprotective effects of low concentrations of thrombin in the
cytokine-stimulated endothelial cells.
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In-San Kim, M.D. Ph.D.
CURRENT ADDRESS
Cell & Matrix Research Institute
Department of Biochemistry and Cell Biology
School of Medicine, Kyungpook National University
101 Dongin-dong, Jung-gu, Daegu 700-422, Korea
EDUCATION
1984 B. Med(M.D)
School of Medicien, Kyungpook National University
1989 D. Med. Sci(Ph.D.) The Graduate School, Kyungpook National University
ACADEMIC AND PROFESSIONAL APPOINTMENTS
1989-present rofessor, Department of Biochemistry and Cell Biology,
School of Medicine, Kyungpook National University
1994-1996 Research Associate, Department of molecular Genetics,
University of Texas M.D. Anderson Cancer Center
BIBLIOGRAPHY
1) Ha-Jeong Kim, Pan-Kyung Kim, Sang Mun Bae, Hye-Nam Son, Thoudam Debraj Singh,
Jung-Eun Kim, Byung-Heon Lee, Rang-Woon Park, In-San Kim, TGFBIp/βig-h3 activates
platelets and promotes thrombogenesis. Blood, in press. (IF=10.432)
2) Park SY, Jung MY, Kim IS. Stabilin-2 mediates homophilic cell-cell interactions via its
FAS1 domains. FEBS Lett. 2009 Apr 17;583(8):1375-80. Epub 2009 Mar 26.
3) Seung-Yoon Park, Wonjung Kwak, Narendra Tapha, Mi-Yoen Jung, Ju-Ock Nam, In-Seop So,
So-Youn Kim, Jeongsoo Yoo, Jaetae Lee, and In-San Kim, Combination therapy and noninvasive imaging using a dual therapeutic vector expressing sodium iodide symporter
(NIS) and MDR1 shRNA J Nucl Med. 2008 Sep;49(9):1480-1488. Epub 2008 Aug
14.(IF=5.915)
4) Park SY, Kim SY, Jung MY, Bae DJ, Kim IS. Epidermal growth factor-like domain repeat
of stabilin-2 recognizes phosphatidylserine during cell corpse clearance. Mol Cell Biol.
2008 Sep;28(17):5288-98. Epub 2008 Jun 23. (IF=6.420)
5) Mi-Kyung Kwon, Ju-Ock Nam, Rang-Woon Park, Byung-Heon Lee, Jae-Yong Park, YoungRo Byun, Sang-Yoon Kim, Ick-Chan Kwon, and In-San Kim, Antitumor effect of a
transducible fusogenic peptide releasing multiple pro-apoptotic peptides by caspase-3.
Mol. Cancer Ther., 2008 Jun;7(6):1514-22. (IF=4.800)
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A New Mechanism of Rapid Clearance of Apoptotic Cells
In-San Kim
Department of Biochemistry and Cell Biology, Kyungpook National University Medical School
Here, we provide evidence that stabilin-1 & 2 are PS receptors which perform a key function in
the rapid clearance of cell corpses. They recognize PS on apoptotic cells, mediates their engulfment
and releases the anti-inflammatory cytokine, TGF-. At least four tandem repeats of EGF-like
domains are required to recognize PS and the second atypical EGF-like domain in EGFrp is critical for
calcium-dependent PS-recognition. Several adaptor molecules including GULP, thymosin 4,
ARHGAP12 have been identified. Stabilin-1 & -2 in sinus endothelial cells also play a critical role in
capturing aged RBCs and presenting them to macrophages for the efficient clearance of aged RBCs.
Taken together, stabilin-1 & 2 are the membrane PS receptors to provide tethering and tickling
signals for the phagocytosis of apoptotic cells.
15