Abstract
Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.
Highlights
Tumor cells display a variety of antigens including anomalous expression of cancer/testis-associated antigens (CTAs)
We explored whether other genes from the murine Cor1 family such mXLR, mXMR and mSCP3, which share more than 60% homology with human SCP3 (hSCP3), could have similar tumorigenic potential in the NIH3T3 model [10]
We provide the first compelling data that hSCP3 can play a key role in human tumorigenesis
Summary
Tumor cells display a variety of antigens including anomalous expression of cancer/testis-associated antigens (CTAs). CTAs are restricted in normal tissues to germ cells of the testis, with occasional expression in female reproductive organs, and are expressed in histologically different types of malignant human tumors [1,2,3,4]. The tumor restricted expression pattern of CTAs makes them an interesting target for immunotherapeutic approaches [3,5]. The role of CTA expression in tumor cells remains unclear, and is an area of active research. Our results on the expression of CTAs and their molecular mechanism in tumor cells may provide better insight into tumorigenesis. Cor family members such as X-linked lymphocyte regulated protein (XLR), Xlr-related meiosis regulated protein (XMR), and synaptonemal complex protein 3 (SCP3) are typical CTAs [1]
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