SKL2001 suppresses colon cancer spheroid growth through regulation of the E-cadherin/β-Catenin complex

Aberrant activation of Wnt signaling plays a pivotal role in the development of human cancers including colon cancer. Small compounds that regulate Wnt signaling are attractive candidate for the colon cancer therapy. Here, we showed that SKL2001, which has been identified as an activator for Wnt signaling by disrupting the Axin/β-Catenin complex, negatively regulates growth of colon cancer spheroids cultured in the 3D condition that simulates tumor microenvironment in vivo. SKL2001 inhibited proliferation of colon cancer cells cultured in 3D spheroid and induced them accumulation in the G0/G1 phase of the cell cycle with a reduced c-myc level. To examine the potential of arrested cells to recover, colon cancer spheroids that were treated with SKL2001 were then cultured in the SKL2001-free medium. We found that SKL2001-treated cells were resumed cell cycle progression and proliferated in the SKL2001-free medium. Notably, SKL2001 facilitated round-shape spheroid formation. This was associated with upregulated expressions of E-cadherin and β-Catenin. These findings suggest that SKL2001 can suppress colon cancer spheroid growth through regulating cell cycle progression and cadherin/catenin mediated cell-cell contact.