SCC-S2 interacted with LATS1 and abolished Hippo signaling. The expression of phosphorylated LATS1 and YAP was downregulated, and YAP was upregulated by overexpressing SCC-S2 in SW480 cells. Accordingly, the phosphorylation of LATS1 and YAP were increased, and the expression of YAP was decreased after depleting SCC-S2 in HCT116 cells (A). (B) The TEAD luciferase activities were enhanced or inhibited by overexpressing and depressing SCC-S2. SCC-S2 interacted (C) and colocalized with LATS1 (D) in the cytoplasm of CRC cells. After co-transfecting SCC-S2 plasmids together with LATS1-siRNA into CRC cells, the upregulation of CyclinD1, MMP-7, a Active-β-catenin and YAP were counteracted, while the phosphorylated LATS1 and YAP were restored (E). The proliferation (F) and invasion (G) abilities were also decreased. Scale bar = 20 μm. Abbreviations: NC, negative control; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; DAPI, 4′,6-diamidino-2-phenylindole; YAP, yes-associated protein.