LIM-homeobox transcription factor 1, alpha (LMX1A) inhibits tumourigenesis, epithelial-mesenchymal transition and stem-like properties of epithelial ovarian cancer

被引：24

作者：

Chao, Tai-Kuang ^{[1
]}

Yo, Yi Te ^{[2
,4
]}

Liao, Yu-Ping ^{[3
]}

Wang, Yu-Chi ^{[2
]}

Su, Po-Hsuan ^{[4
]}

Huang, Tien-Shuo ^{[1
]}

Lai, Hung-Cheng ^{[2
,3
,4
]}

机构：

[1] Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Pathol, Taipei 114, Taiwan

[2] Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Obstet & Gynecol, Taipei 114, Taiwan

[3] Natl Def Med Ctr, Grad Inst Life Sci, Taipei 114, Taiwan

[4] Natl Def Med Ctr, Lab Epigenet & Canc Stem Cells, Taipei 114, Taiwan

来源：

GYNECOLOGIC ONCOLOGY | 2013年 / 128卷 / 03期

关键词：

Chemosensitivity; Epigenetic; Epithelial ovarian cancer; LMX1A; Methylation; Stem cell; SURFACE EPITHELIUM; E-CADHERIN; TUMOR PROGRESSION; DRUG-RESISTANCE; CERVICAL-CANCER; CELLS; CARCINOMA; EXPRESSION; PATHOGENESIS; DISTINCT;

D O I：

10.1016/j.ygyno.2012.12.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Objective. We reported recently the hypermethylation of LMX1A, a LIM-homeobox gene, as a prognostic biomarker in ovarian cancer; however, the function of LMX1A in ovarian cancer remains unknown. The present study aimed to evaluate the hypothesized tumour-suppressor functions of LMX1A in ovarian cancer. Methods. We analysed the function of LMX1A by examining cell lines, animal models and human ovarian cancer tissues. Overexpression of LMX1A in relation to chemotherapy was also analysed. Results. The expression of LMX1A inhibited cell proliferation, migration, invasion and colony formation in vitro, as well as tumourigenicity in a xenotransplantation mouse model. LMX1A also sensitized ovarian cancer cell lines to chemotherapeutics, and affected epithelial-mesenchymal transition (EMT). The restoration of LMX1A down-regulated stem cell markers and inhibited tumour spheroid formation in SKOV3 cells. Univariate analysis of immunohistochemical staining of tissue arrays (n = 83) revealed that low LMX1A expression was significantly associated with advanced stages (p = 0.001), poor differentiation (p<0.001), early recurrence (p = 0.023) and poor overall survival (p = 0.042) in ovarian cancer. Conclusions. The present study demonstrated, for the first time, that LMX1A is a bona fide tumour suppressor of ovarian cancer. The prognostic values of LMX1A may provide a biomarker for personalized treatments of ovarian cancer patients. The mechanisms of LMX1A in EMT and stem-like properties in ovarian cancer warrant further investigation. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：475 / 482

页数：8

共 62 条

[1] Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas: An exception to the norm [J].

Ahmed, Nuzhat ;

Thompson, Erik W. ;

Quinn, Michael A. .

JOURNAL OF CELLULAR PHYSIOLOGY, 2007, 213 (03) :581-588

[2] Ovarian surface epithelium: Biology, endocrinology, and pathology [J].

Auersperg, N ;

Wong, AST ;

Choi, KC ;

Kang, SK ;

Leung, PCK .

ENDOCRINE REVIEWS, 2001, 22 (02) :255-288

[3] Epigenetic regulation of CD133 and tumorigenicity of CD133+ovarian cancer cells [J].

Baba, T. ;

Convery, P. A. ;

Matsumura, N. ;

Whitaker, R. S. ;

Kondoh, E. ;

Perry, T. ;

Huang, Z. ;

Bentley, R. C. ;

Mori, S. ;

Fujii, S. ;

Marks, J. R. ;

Berchuck, A. ;

Murphy, S. K. .

ONCOGENE, 2009, 28 (02) :209-218

[4] Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer [J].

Bapat, SA ;

Mali, AM ;

Koppikar, CB ;

Kurrey, NK .

CANCER RESEARCH, 2005, 65 (08) :3025-3029

[5] The biology of ovarian cancer: new opportunities for translation [J].

Bast, Robert C., Jr. ;

Hennessy, Bryan ;

Mills, Gordon B. .

NATURE REVIEWS CANCER, 2009, 9 (06) :415-428

[6] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[7] Cancer stem cells and EMT in carcinoma [J].

Biddle, Adrian ;

Mackenzie, Ian C. .

CANCER AND METASTASIS REVIEWS, 2012, 31 (1-2) :285-293

[8] Cancer Stem Cells in Squamous Cell Carcinoma Switch between Two Distinct Phenotypes That Are Preferentially Migratory or Proliferative [J].

Biddle, Adrian ;

Liang, Xiao ;

Gammon, Luke ;

Fazil, Bilal ;

Harper, Lisa J. ;

Emich, Helena ;

Costea, Daniela Elena ;

Mackenzie, Ian C. .

CANCER RESEARCH, 2011, 71 (15) :5317-5326

[9] Correlation of Snail expression with histological grade and lymph node status in breast carcinomas [J].

Blanco, MJ ;

Moreno-Bueno, G ;

Sarrio, D ;

Locascio, A ;

Cano, A ;

Palacios, J ;

Nieto, MA .

ONCOGENE, 2002, 21 (20) :3241-3246

[10] Opinion - Migrating cancer stem cells - an integrated concept of malignant tumour progression [J].

Brabletz, T ;

Jung, A ;

Spaderna, S ;

Hlubek, F ;

Kirchner, T .

NATURE REVIEWS CANCER, 2005, 5 (09) :744-749

← 1 2 3 4 5 6 7 →