SUSD2 promotes cancer metastasis and confers cisplatin resistance in high grade serous ovarian cancer
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan, Shandong (China)
- Institute of Diagnostics,School of Medicine, Shandong University, Ji'nan, Shandong 250012 (China)
Highlights: • SUSD2 was one of Notch3 downstream genes in high grade serous ovarian cancer (HGSOC). • High expression of SUSD2 was associated with poor prognosis in HGSOC. • Over-expression of SUSD2 can promote ovarian cancer cells metastasis via inducing EMT. • SUSD2 down-regulating E-cadherin and promoting migration were triggered by EpCAM. • Over-expression of SUSD2 could confer ovarian cancer cells cisplatin resistance through enhancing autophagy. The activation of Notch3 is associated with potential progression of ovarian cancer, tumor invasion, metastasis and chemoresistance, which account for poor prognosis of high grade serous ovarian cancer (HGSOC). However, the underlying mechanisms of Notch3 are not yet very clear. Here we show that SUSD2 is one of Notch3-regulating genes and the elevated protein expression of SUSD2 in HGSOC. We also found that its high expression level was significantly correlated with worse overall survival, early recurrence and lymph nodes metastasis. Moreover, overexpression of SUSD2 in ovarian cancer cells promoted epithelial-mesenchymal transition (EMT) and the metastatic capacity of malignant cells. In contrast, silencing SUSD2 in aggressive ovarian cancer cells inhibited these processes both in vitro and in vivo. Mechanistically, we found SUSD2 promoted EMT through regulating the expression of EpCAM and EpCAM silencing reversed SUSD2-induced E-cadherin reduction and cells migration. Further experiments indicated a role of SUSD2 in conferring cisplatin resistance in ovarian cancer probably through enhancing autophagy in vitro. Collectively, these findings shed a new insight into the role of Notch3 downstream gene SUSD2 and provided a new therapeutic target for HGSOC.
- OSTI ID:
- 23082450
- Journal Information:
- Experimental Cell Research, Vol. 363, Issue 2; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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