The TMEFF2 tumor suppressor modulates integrin expression, RhoA activation and migration of prostate cancer cells

被引:17
作者
Chen, Xiaofei [1 ]
Corbin, Joshua M. [2 ]
Tipton, Greg J. [2 ]
Yang, Li V. [2 ,3 ,4 ]
Asch, Adam S. [2 ,3 ]
Ruiz-Echevarria, Maria J. [2 ,3 ,4 ]
机构
[1] E Carolina Univ, Brody Sch Med, Dept Biochem & Mol Biol, Greenville, NC 27834 USA
[2] E Carolina Univ, Brody Sch Med, Dept Oncol, Greenville, NC 27834 USA
[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[4] E Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, Greenville, NC 27834 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2014年 / 1843卷 / 06期
关键词
TMEFF2; Integrin; Cell migration; Cell attachment; Prostate cancer; GROWTH-FACTOR; BREAST-CANCER; METASTASIS; PROTEIN; GENE; ALPHA(V)BETA(3); PROGRESSION; ADHESION;
D O I
10.1016/j.bbamcr.2014.03.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Cell adhesion and migration play important roles in physiological and pathological states, including embryonic development and cancer invasion and metastasis. The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is expressed mainly in brain and prostate and its expression is deregulated in prostate cancer. We have previously shown that TMEFF2 can function as a tumor suppressor by inhibiting cell migration and invasion of prostate cells. However, the molecular mechanisms involved in this inhibition are not clear. In this study we demonstrate that TIVIEFF2 affects cell adhesion and migration of prostate cancer cells and that this effect correlates with changes in integrin expression and RhoA activation. Deletion of a 13 basic-rich amino acid region in the cytoplasmic domain of TMEFF2 prevented these effects. Overexpression of TMEFF2 reduced cell attachment and migration on vitronectin and caused a concomitant decrease in RhoA activation, stress fiber formation and expression of alpha v,beta 1and beta 3 integrin subunits. Conversely, TMEFF2 interference in 22Rv1 prostate cancer cells resulted in an increased integrin expression. Results obtained with a double TRAMP/TMEFF2 transgenic mouse also indicated that TMEFF2 expression reduced integrin expression in the mouse prostate. In summary, the data presented here indicate an important role of TMEFF2 in regulating cell adhesion and migration that involves integrin signaling and is mediated by its cytoplasmic domain. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:1216 / 1224
页数:9
相关论文
共 48 条
[1]
Afar DEH, 2004, MOL CANCER THER, V3, P921
[2]
Phorbol ester-induced shedding of the prostate cancer marker transmembrane protein with epidermal growth factor and two follistatin motifs 2 is mediated by the disintegrin and metalloproteinase-17 [J].
Ali, Nazim ;
Knaeuper, Vera .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (52) :37378-37388
[3]
Regulation of nodal and BMP signaling by tomoregulin-1 (X7365) through novel mechanisms [J].
Chang, CB ;
Eggen, BJL ;
Weinstein, DC ;
Brivanlou, AH .
DEVELOPMENTAL BIOLOGY, 2003, 255 (01) :1-11
[4]
Chen Xiaofei, 2013, Int J Biochem Mol Biol, V4, P83
[5]
The Tumor Suppressor Activity of the Transmembrane Protein with Epidermal Growth Factor and Two Follistatin Motifs 2 (TMEFF2) Correlates with Its Ability to Modulate Sarcosine Levels [J].
Chen, Xiaofei ;
Overcash, Ryan ;
Green, Thomas ;
Hoffman, Donald ;
Asch, Adam S. ;
Ruiz-Echevarra, Maria J. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (18) :16091-16100
[6]
The role of αvβ3 in prostate cancer progression [J].
Cooper, CR ;
Chay, CH ;
Pienta, KJ .
NEOPLASIA, 2002, 4 (03) :191-194
[7]
Integrin signaling to the actin cytoskeleton [J].
DeMali, KA ;
Wennerberg, K ;
Burridge, K .
CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (05) :572-582
[8]
Integrins in cancer: biological implications and therapeutic opportunities [J].
Desgrosellier, Jay S. ;
Cheresh, David A. .
NATURE REVIEWS CANCER, 2010, 10 (01) :9-22
[9]
Association of αvβ3 integrin expression with the metastatic potential and migratory and chemotactic ability of human osteosarcoma cells [J].
Duan, XP ;
Jia, SF ;
Zhou, ZC ;
Langley, RR ;
Bolontrade, MF ;
Kleinerman, ES .
CLINICAL & EXPERIMENTAL METASTASIS, 2004, 21 (08) :747-753
[10]
FOCAL ADHESIONS: NEW ANGLES ON AN OLD STRUCTURE [J].
Dubash, Adi D. ;
Menold, Marisa M. ;
Samson, Thomas ;
Boulter, Etienne ;
Garcia-Mata, Rafael ;
Doughman, Renee ;
Burridge, Keith .
INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY, VOL 277, 2009, 277 :1-65