SCC-S2 Facilitates Tumor Proliferation and Invasion via Activating Wnt Signaling and Depressing Hippo Signaling in Colorectal Cancer Cells and Predicts Poor Prognosis of Patients.

SCC-S2 overexpression has been implicated in several human cancers, its correlation with prognosis and the mechanism how it reserved biological roles are still uncertain. The current study demonstrated that, in 142 archived colorectal carcinoma (CRC) tissue samples, SCC-S2 expression was significantly correlated with higher histological grade ( p=0.001), tumor invasion ( p=0.001), advanced Dukes staging ( p=0.002), positive regional lymph node metastasis ( p=0.024), and poor overall survival ( p<0.001). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Transwell assays showed that SCC-S2 significantly promoted the proliferation and invasion. SCC-S2 expression was also accompanied by the overexpression CyclinD1, matrix metalloproteinase-7 (MMP-7), active-β-catenin, yes-associated protein (YAP), and connective tissue growth factor (CTGF), as well as the depression of p-large tumor suppressor kinase 1 (p-LATS1) and p-YAP. Moreover, SCC-S2 interacted and colocalized with LATS1, the interaction may interrupt Hippo signaling and thereafter activate canonical Wnt signaling. In conclusion, our data suggested that SCC-S2 was associated with the progression and unfavorable prognosis of CRCs. Meanwhile, SCC-S2 facilitated canonical Wnt signaling and its downstream effectors (CyclinD1, MMP-7) and promoted tumor proliferation and invasion, which depended on the inhibition of Hippo signaling induced by SCC-S2-LATS1 interaction. These results indicated that SCC-S2 might be used as a novel target for the prevention and treatment of colorectal cancer.

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