分泌型磷蛋白-1通过激活β-catenin信号促进结直肠癌进展

Abstract

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.