Abstract
SPTBN1 plays an anticancer role in many kinds of tumors and participates in the chemotherapeutic resistance of epithelial ovarian cancer (EOC). Here, we reported that lower SPTBN1 expression was significantly related to advanced EOC stage and shorter progression-free survival. SPTBN1 expression was also higher in less invasive EOC cell lines. Moreover, SPTBN1 decreased the migration ability of the EOC cells A2780 and HO8910 and inhibited the growth of EOC cells in vitro and tumor xenografts in vivo. SPTBN1 suppression increased the epithelial mesenchymal transformation marker Vimentin while decreasing E-cadherin expression. By analyzing TCGA data and immunohistochemistry staining of tumor tissue, we found that SPTBN1 and SOCS3 were positively coexpressed in EOC patients. SOCS3 overexpression or JAK2 inhibition decreased the proliferation and migration of EOC cells as well as the expression of p-JAK2, p-STAT3 and Vimentin, which were enhanced by the downregulation of SPTBN1, while E-cadherin expression was also reversed. It was also verified in mouse embryonic fibroblasts (MEFs) that loss of SPTBN1 activated the JAK/STAT3 signaling pathway with suppression of SOCS3. Our results suggest that SPTBN1 suppresses the progression of epithelial ovarian cancer via SOCS3-mediated blockade of the JAK/STAT3 signaling pathway.
Highlights
Epithelial ovarian cancer (EOC) is the third most common gynecological tumor with the highest mortality rate
By analyzing The Cancer Genome Atlas (TCGA) data, we found that the expression of SPTBN1 was significantly decreased as EOC staging increased (Figure 1A)
The results showed that overexpression of suppressor of cytokine signaling 3 (SOCS3) reversed the levels of p-JAK2 and p-STAT3, which were enhanced by SPTBN1 inhibition in HO8910 (Figure 5A, left) and A2780 cells (Supplementary Figure 2)
Summary
Epithelial ovarian cancer (EOC) is the third most common gynecological tumor with the highest mortality rate. SPTBN1 is an adaptor protein for Smad3/Smad complex formation in the TGF-β signaling pathway, thereby participating in cell cycle regulation [8]. It has been reported that SPTBN1 plays an important role in the pathogenesis and progression of many tumors, such as liver cancer [5,6,7, 9, 10], lung cancer [11,12,13,14], pancreatic cancer [15] and colon cancer [16, 17]. The effects of SPTBN1 on the growth and metastasis of epithelial ovarian cancer and the specific mechanism have rarely been reported and need to be further studied
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