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

Tai Kuang Chao, Yi Te Yo, Yu Ping Liao, Yu Chi Wang, Po Hsuan Su, Tien Shuo Huang, Hung Cheng Lai

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)475-482
Number of pages8
JournalGynecologic Oncology
Volume128
Issue number3
DOIs
Publication statusPublished - Mar 2013
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Homeobox Genes
Ovarian Neoplasms
Transcription Factors
Biomarkers
Ovarian epithelial cancer
Cell Line
Heterologous Transplantation
Tumor Biomarkers
Cell Movement
Neoplasms
Stem Cells
Animal Models
Cell Proliferation
Staining and Labeling
Recurrence
Drug Therapy
Survival

Keywords

  • Chemosensitivity
  • Epigenetic
  • Epithelial ovarian cancer
  • LMX1A
  • Methylation
  • Stem cell

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

LIM-homeobox transcription factor 1, alpha (LMX1A) inhibits tumourigenesis, epithelial-mesenchymal transition and stem-like properties of epithelial ovarian cancer. / Chao, Tai Kuang; Yo, Yi Te; Liao, Yu Ping; Wang, Yu Chi; Su, Po Hsuan; Huang, Tien Shuo; Lai, Hung Cheng.

In: Gynecologic Oncology, Vol. 128, No. 3, 03.2013, p. 475-482.

Research output: Contribution to journalArticle

Chao, Tai Kuang ; Yo, Yi Te ; Liao, Yu Ping ; Wang, Yu Chi ; Su, Po Hsuan ; Huang, Tien Shuo ; Lai, Hung Cheng. / LIM-homeobox transcription factor 1, alpha (LMX1A) inhibits tumourigenesis, epithelial-mesenchymal transition and stem-like properties of epithelial ovarian cancer. In: Gynecologic Oncology. 2013 ; Vol. 128, No. 3. pp. 475-482.
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AU - Su, Po Hsuan

AU - Huang, Tien Shuo

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N2 - 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.

AB - 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.

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