Secreted phosphoprotein-1 accelerates the progression of human colorectal cancer through activating β-catenin signaling

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract and one of the leading causes of cancer-associated mortality. Secreted phosphoprotein-1 (SPP-1) is overexpressed in CRC and promotes cancer progression, but the underlying mechanisms underlying SPP-1 function remain unclear. The present study aimed to explore the effects of Wnt/β-catenin signaling in SPP-1-induced CRC progression. The expression patterns of SPP-1 in CRC tissues were examined using reverse transcription-quantitative (RT-q)PCR, western blotting and immunohistochemistry. SPP-1 expression in cells was assessed using RT-qPCR and western blotting. Cell-Counting Kit-8, flow cytometry and tumor-burdened mice experiments were used to determine cell proliferation, apoptosis and in vivo tumor formation abilities. The results showed that SPP-1 expression was markedly elevated in CRC tissues and cells compared with that in normal colorectal tissues and cells. High expression of SPP-1 was associated with advanced clinical process and low overall survival rate in patients with CRC. Besides, SPP-1 could interact with β-catenin and positively regulated β-catenin protein expression, and enhanced its nuclear accumulation. Moreover, SPP-1-upregulation significantly enhanced cell proliferation and in vivo tumor formation ability, and reduced apoptosis, whereas these effects were all abolished when β-catenin was silenced. Overall, the present study revealed that SPP-1 promoted the progression of CRC in a β-catenin-dependent manner.