Protein tyrosine phosphatase PTPN3 promotes drug resistance and stem cell-like characteristics in ovarian cancer.

Abstract:

:The current standard treatment for ovarian cancer is aggressive surgery followed by platinum-based combination chemotherapy. Recurrence and chemotherapeutic drug resistance are the two main factors that account for the high mortality of most ovarian cancers. Liposomal doxorubicin is primarily used for the treatment of ovarian cancer when the disease has progressed after platinum-based chemotherapy. However, relatively little is known about the genomic changes that contribute to both cisplatin and doxorubicin resistance in high-grade serous ovarian cancer (HGSC) under the selective pressure of chemotherapy. Here, we found that protein tyrosine phosphatase PTPN3 gene expression was substantially increased in both cisplatin and doxorubicin-resistant ovarian cancer cells. Silencing of PTPN3 restored sensitivity to cisplatin and doxorubicin in resistant ovarian cancer cells. Down-regulation of PTPN3 also inhibited cell cycle progression, migration, stemness in vitro and the tumorigenicity of resistant ovarian cancer cells in vivo. Meanwhile, the expression of PTPN3 was found to be regulated by miR-199 in resistant ovarian cancer cells. These findings suggest that PTPN3 promotes tumorigenicity, stemness and drug resistance in ovarian cancer, and thus is a potential therapeutic target for the treatment of ovarian cancer.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Li S,Cao J,Zhang W,Zhang F,Ni G,Luo Q,Wang M,Tao X,Xia H

doi

10.1038/srep36873

subject

Has Abstract

pub_date

2016-11-11 00:00:00

pages

36873

issn

2045-2322

pii

srep36873

journal_volume

6

pub_type

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