S100A10 silencing suppresses proliferation, migration and invasion of ovarian cancer cells and enhances sensitivity to carboplatin

Abstract

BackgroundOvarian cancer is the leading cause of gynecological cancer-related mortality. The novel oncogene S100A10 has been reported to be involved in cancer cell proliferation, invasion and metastasis. The role of S100A10 in ovarian cancer has not been well studied and the effect of S100A10 on chemotherapy remains unclear. The aims of the present study were to investigate the functional role of S100A10 in the progression and carboplatin sensitivity of ovarian cancer.MethodsWe examined the expression levels in tissues of S100A10 in 138 cases of ovarian cancer by IHC. To determine the functional roles of downregulated S100A10 in ovarian cancer, cell proliferation, colony formation, cell migration and invasion assays were performed. Chemoresistance was analyzed by apoptosis assay. A xenograft tumor model was established to confirm the role of S100A10 in carboplatin resistance in vivo. Using Western blot assays, we also explored the possible mechanisms of S100A10 in ovarian cancer.ResultsThe results showed that increased expression of S100A10 was positively associated with carboplatin resistance (P < 0.001), tumor grade (P = 0.048) and a poorer prognosis (P = 0.0053). Functional analyses demonstrated that S100A10 suppression significantly suppressed ovarian cancer cell proliferation, colony formation, cell migration and invasion, remarkably increased carboplatin-induced apoptosis in SKOV3 and A2780 cells and inhibited tumor growth in vivo. Downregulation of S100A10 expression could inhibit cell proliferation and enhance ovarian cancer cell sensitivity to carboplatin, possibly involving the regulation of cleaved-Caspase3 and cleaved-PARP.ConclusionsTogether, the results of the present study reveal that S100A10 expression can be used as a predictive marker for the prognosis of ovarian cancer and chemosensitivity to carboplatin.

S100 Calcium Binding Protein A10, A Novel Oncogene, Promotes the Proliferation, Invasion, and Migration of Hepatocellular Carcinoma

“…Additionally, S100A10 also regulated the metastasis of lung cancer cells by the interaction with DLC1 (Yang et al, 2011). Recently, Cui's group reported that S100A10 was an oncogene in ovarian cancer by promoting tumor metastasis, and reduced sensitivity to carboplatin (Wang et al, 2019b). In our study, we found that S100A10 promoted the migration and invasion of Hep3B cells.…”

“…The abnormal expression of S100A10 affects cell proliferation, apoptosis, angiogenesis, inflammation, and invasion. Numerous studies have confirmed that S100A10 is an oncogene, such as intestinal cancer (Suzuki et al, 2011), basal-type breast cancer (McKiernan et al, 2011), lung cancer (Katono et al, 2016), ovarian cancer (Wang et al, 2019b), pancreatic ductal cancer (Bydoun et al, 2018), and gastric cancer (El-Rifai et al, 2002). S100A10 has also been noted in HCC (Kittaka et al, 2008;Shan et al, 2013;Zhang et al, 2016;Lou et al, 2019).…”

Upregulation of S100A10 in metastasized breast cancer stem cells

“…The fact that upregulation of S100A10 was characteristically observed in the CD44 + breast cancer cells but not in CD44breast cancer cells among the metastasized cells in the liver ( Figure 1C) further supports a notion that S100A10 has specific roles in the regulation of the metastasis of breast cancer CSCs in vivo. Although S100A10 promotes multiple oncogenic properties including proliferation, invasion, and migration especially in ovarian cancers, 38,39 the effect of S100A10 on proliferation and migration was not evident in breast cancer cells and PDX cells, suggesting that the effect of S100A10 on oncogenic properties is cell type-dependent ( Figure S2-S6).…”

Plasmin and Plasminogen System in the Tumor Microenvironment: Implications for Cancer Diagnosis, Prognosis, and Therapy

“…For example, loss of p11 in ovarian cancer cells resulted in reduced tumor growth in NOD/SCID mice In Vivo with concurrent reduction of cell proliferation, colony formation, migration, and invasion In Vitro. Moreover, p11-depleted cells show decreased resistance to carboplatin In Vitro [209]. Li Y et al, recently demonstrated the importance of p11 in gastric cancer tumorigenesis.…”