<p>SPOP Regulates The Biological Mechanism Of Ovarian Cancer Cells Through The Hh Signaling Pathway</p>

Abstract

BackgroundOvarian cancer is characterized by high metastatic potential and high mortality. More than 80% of primary ovarian malignancies are epithelial ovarian cancers. There is increasing evidence that Speckle-type POZ protein (SPOP) is highly correlated with the development of various types of cancer. However, the effects of SPOP on epithelial ovarian cancer and the associated molecular mechanisms remain unclear.Materials and methodsWe compared SPOP expression between epithelial ovarian cancer tissues and normal ovarian tissues by using immunohistochemical staining. To determine the role of SPOP in epithelial ovarian cancer cells, we overexpressed or knocked down SPOP in the epithelial ovarian cancer cell line OVCAR-3 using lentiviral vectors.ResultsOur results from the present study indicated that SPOP expression was significantly downregulated in human epithelial ovarian cancer and was associated with the FIGO stage and the histopathologic grading of the tumor. The overexpression and knockdown experiments revealed that SPOP inhibited proliferation while promoting apoptosis in ovarian cancer cells. Inhibition of SPOP mis-activated the Hedgehog (Hh) signaling pathway, thereby inhibiting apoptosis in ovarian cancer cells.ConclusionSPOP suppresses proliferation and promotes apoptosis in human ovarian cancer cells by inhibiting the Hh signaling pathway, offering the possibility of new approaches for the treatment of ovarian cancer.

CUL3/SPOP complex prevents immune escape and enhances chemotherapy sensitivity of ovarian cancer cells through degradation of PD-L1 protein

“…31 Consistent with our findings, a reduction in SPOP has also been demonstrated in human epithelial ovarian cancer, and its high expression leads to suppressed cancer cell proliferation. 9 …”

“…31 Consistent with our findings, a reduction in SPOP has also been demonstrated in human epithelial ovarian cancer, and its high expression leads to suppressed cancer cell proliferation. 9 Further to explore the downstream mechanisms, we unraveled that CUL3 degraded PD-L1 protein by forming a complex with SPOP. CUL3/SPOP complex inhibited the immune escape of ovarian cancer cells and improved the chemotherapy sensitivity of ovarian cancer cells.…”

“… 8 More importantly, speckle type POZ protein (SPOP), a substrate recognition receptor for CUL3/RING type ubiquitin E3 complex, is capable of inhibiting proliferation and promoting apoptosis of human ovarian cancer cells by blockage of Hh signaling pathway, which provides a new approach for ovarian cancer treatment. 9 10 …”

Clinicopathological and prognostic significance of speckle-type POZ protein in cancers: a systematic review and meta-analysis

“…Finally, as shown in Fig. 1 , a total of 14 studies [ 9 – 11 , 20 – 30 ] were eligible for this meta-analysis, which contained 2582 cases from 3 different countries (China, USA, and Korea) and were published from 2009 to 2020. Among them, more than 8 cancer types were investigated, including prostate cancer, ovarian cancer, renal cancer, gastric cancer, liver cancer, lung cancer, glioma and colorectal cancer.…”

The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis

“…Additionally, SPOP transfection downregulated proliferating cell nuclear antigen (PCNA) and antiapoptotic protein BCL2 and upregulated proapoptotic proteins cleaved-caspase3 and Bax expression, while SPOP knockdown produced the opposite effects. Interestingly, low SPOP levels contributed to enhanced Hh signaling by modulating GLI1/2 expression, resulting in decreased apoptosis in ovarian cancer cell lines [ 123 ].…”