Huwe1 inactivation promotes ovarian cancer metastasis by extracellular matrix deregulation

Abstract

Objective: Huwe1 is critical for promoting the progression of a range of malignancies including ovarian cancer. Still, its role in ovarian cancermetastasis has not been reported. The goal of our studywas to evaluate a correlation betweenHuwe1 and ovarian cancer metastasis. Methods: The mouse ovary surface epithelium (MOSE) cells isolated from Huwe1 mice were identified by flow cytometry assay. Cell migration and invasion were analyzed by transwell system. The molecular mechanism of Huwe1 in ovarian cancer migration and invasion was explored by analyzing the difference of RNAseq data between MOSE-Huwe1-CreER and MOSE-Huwe1-Cre cells. Results: Huwe1 deletion significantly promoted tumor migration and invasion in ovarian cancer cells. Moreover, tumor cells were more frequently detected in the blood when the mice bearing allografts were treated with tamoxifen. Transcriptome analysis indicated that this phenotype may be due to the alteration in cell adhesion caused by the Huwe1 knockout. Conclusion: Huwe1 inactivation promoted ovarian cancer metastasis by the extracellular matrix (ECM) deregulation.