WNT-1 inducible signaling pathway protein-1 enhances growth and tumorigenesis in human breast cancer.
WNT1 inducible signaling pathway protein 1 (WISP1) plays a key role in many cellular functions in a highly tissue-specific manner; however the role of WISP1 in breast cancer is still poorly understood. Here, we demonstrate that WISP1 acts as an oncogene in human breast cancer. We demonstrated that human breast cancer tissues had higher WISP1 mRNA expression than normal breast tissues and that treatment of recombinant WISP1 enhanced breast cancer cell proliferation. Further, ectopic expression of WISP1 increased the growth of breast cancer cells in vitro and in vivo. WISP1 transfection also induced epithelial-mesenchymal-transition (EMT) in MCF-7 cells, leading to higher migration and invasion. During this EMT-inducing process, E-cadherin was repressed and N-cadherin, snail, and β-catenin were upregulated. Filamentous actin (F-actin) remodeling and polarization were also observed after WISP1 transfection into MCF-7 cells. Moreover, forced overexpression of WISP1 blocked the expression of NDRG1, a breast cancer tumor suppressor gene. Our study provides novel evidence that WISP1-modulated NDRG1 gene expression is dependent on a DNA fragment (-128 to +46) located within the human NDRG1 promoter. Thus, we concluded that WISP1 is a human breast cancer oncogene and is a potential therapeutic target.
General Surgery Department, Chang Gung Memorial Hospital and Chang Gung University, 222, Mai-Chin Road, Keelung, Taiwan, 204, R.O.C.
Kun-Chun
KC
Chiang
General Surgery Department, Chang Gung Memorial Hospital and Chang Gung University, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan, 333, R.O.C.
Chun-Nan
CN
Yeh
Department of Anatomy, School of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan, Taiwan, 333, R.O.C.
Li-Chuan
LC
Chung
Department of Nursing, School of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan, Taiwan, 333, R.O.C.
Tsui-Hsia
TH
Feng
Department of Ophthalmology, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, Taiwan, 204, R.O.C.
Chi-Chin
CC
Sun
General Surgery Department, Chang Gung Memorial Hospital and Chang Gung University, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan, 333, R.O.C.
Miin-Fu
MF
Chen
General Surgery Department, Chang Gung Memorial Hospital and Chang Gung University, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan, 333, R.O.C.
Yi-Yin
YY
Jan
General Surgery Department, Chang Gung Memorial Hospital and Chang Gung University, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan, 333, R.O.C.
Ta-Sen
TS
Yeh
General Surgery Department, Chang Gung Memorial Hospital and Chang Gung University, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan, 333, R.O.C.
Shin-Cheh
SC
Chen
Department of Anatomy, School of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan, Taiwan, 333, R.O.C.
Horng-Heng
HH
Juang
D000199:Actins / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D061986:MCF-7 Cells; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D000099259:N-myc Downstream-Regulated Gene 1 Protein
D000199:Actins; D055511:CCN Intercellular Signaling Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C116396:CCN4 protein, human