Synaptonemal complex protein 3 is a prognostic marker in cervical cancer

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.

Synaptonemal complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer patients with lymph node metastasis

“…Among the known signaling pathways, the AKT pathway is a major candidate because it plays a pivotal role in transformation by inducing cell survival, proliferation, invasion, migration and angiogenesis [42,43]. In prior study, we demonstrated that phospho-AKT levels were increased in SCP3-expressing cervical cell lines [11] and that SCP3 mediates an oncogenic phenotype of cervical cancer cells through an AKT-dependent pathway [12]. Further study is needed to demonstrate the details of SCP3's involvement in lymphangiogenesis and whether there is any link between the up-regulation of lymphangiogenetic factors (VEGF-C and VEGF-D) and the AKT pathway.…”

“…In prior study, we have shown that SCP3 overexpression was associated with T factor in the early stage of NSCLC patients [13]. Recent study have showed that SCP3 overexpression is associated with poor prognosis of patients with cervical cancer [12]. However, the association of SCP3 with VEGF-C, VEGF-D and lymphangiogenesis is unknown.…”

“…Although SCP3 expression is highly restricted in the nucleus of meiotic germ cells, ectopic SCP3 expression is frequently observed in human cancers, such as acute lymphoblastic leukemia and cervical cancer [10,11]. We previously demonstrated that SCP3 was significantly associated with cervical cancer progression and LN metastasis of cervical cancer [12], while SCP3 has been defined as a negative prognostic factor in the early stage of NSCLC by immunohistochemistry (IHC) and manual visual scoring [13]. This discrepancy may be explained by the subjectivity of assessing SCP3 positivity.…”

Synaptonemal complex proteins modulate the level of genome integrity in cancers

“…Although the SC proteins were first considered to be expressed only in meiotic cells, accumulating evidence shows that the SC proteins are ectopically and aberrantly expressed in various human cancers, as summarized in Table 1 15‐42 . This evidence suggests that the SC proteins are so‐called cancer/testis antigens, whose expression is normally limited to the germ cells but can be activated in cancer by a demethylation‐dependent process 43 …”

Reconstitution of a flexible SYCP3-DNA fibre suggests a mechanism for SYCP3 coating of the meiotic chromosome axis

“…Sycp3 gene knockout causes infertility in male mice and reduced fertility in females, due to aneuploidy in oocytes and ensuing embryonic lethality (8,19), and a mutation that renders SYCP3 defective causes human male infertility (20). Overexpression of SYCP3 has been reported in some types of cancer (21,22). In SYCP3-null male mice, the LE and SC do not form and homologous chromosomes fail to achieve full synapsis (8,16,23).…”