GLIS1 in Cancer-Associated Fibroblasts Regulates the Migration and Invasion of Ovarian Cancer Cells

A cancer-associated fibroblasts (CAFs) are the most important players that modulate tumor aggressiveness. In this study, we aimed to identify CAF-related genes in ovarian serous carcinomas (OSC) that account for the high incidence and mortality of ovarian cancers (OCs) and to develop therapeutic tar...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-02, Vol.23 (4), p.2218
Main Authors: Kim, Mi Joung, Jung, Daun, Park, Joo Youn, Lee, Seung Min, An, Hee Jung
Format: Article
Language:English
Subjects:
Angiogenesis
Cancer-Associated Fibroblasts - pathology
Carcinoma, Ovarian Epithelial - genetics
Carcinoma, Ovarian Epithelial - pathology
Cell adhesion & migration
Cell growth
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
DNA microarrays
DNA-Binding Proteins - genetics
Female
Fibroblasts
Gene expression
Gene Expression Regulation, Neoplastic - genetics
Genes
Humans
In vivo methods and tests
Metastases
Metastasis
MicroRNAs - genetics
Neoplasm Invasiveness - genetics
Neoplasm Invasiveness - pathology
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
Protein expression
Proteins
Therapeutic applications
Therapeutic targets
Transcription Factors - genetics
Tumor microenvironment
Tumor Microenvironment - genetics
Tumors
Wound healing
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Summary:A cancer-associated fibroblasts (CAFs) are the most important players that modulate tumor aggressiveness. In this study, we aimed to identify CAF-related genes in ovarian serous carcinomas (OSC) that account for the high incidence and mortality of ovarian cancers (OCs) and to develop therapeutic targets for tumor microenvironment modulation. Here, we performed a microarray analysis of CAFs isolated from three metastatic and three nonmetastatic OSC tissues and compared their gene expression profiles. Among the genes increased in metastatic CAFs (mCAFs), GLIS1 (Glis Family Zinc Finger 1) showed a significant increase in both the gene mRNA and protein expression levels. Knockdown of GLIS1 in mCAFs significantly inhibited migration, invasion, and wound healing ability of OC cells. In addition, an in vivo study demonstrated that knockdown of GLIS1 in CAFs reduced peritoneal metastasis. Taken together, these results suggest that CAFs support migration and metastasis of OC cells by GLIS1 overexpression. It also indicates GLIS1 in CAFs might be a potential therapeutic target to inhibit OC metastasis.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23042218