Tumour suppressor ABCA8 inhibits malignant progression of colorectal cancer via Wnt/β-catenin pathway

Abstract

BackgroundColorectal cancer (CRC) is one of the most commonly diagnosed malignant tumours of the digestive tract, and new therapeutic targets and prognostic markers are still urgently required. However, the role and molecular mechanisms of ATP binding cassette subfamily A member 8 (ABCA8) in CRC remain unclear. MethodsDatabases and clinical specimens were analysed to determine the expression level of ABCA8 in CRC. Colony formation, CCK-8 and Transwell assays were conducted to determine cell proliferation, viability, migration and invasion. Flow cytometry was used to detect cell cycle progression and apoptosis. Western blot and rescue experiments were performed to determine the specific mechanisms of action of ABCA8. ResultsABCA8 expression is dramatically down-regulated in CRC tissues and cell lines. Ectopic expression of ABCA8 induced apoptosis and cell cycle arrest in vitro, inhibited cell growth, suppressed migration and invasion, reversed epithelial-mesenchymal transition and suppressed xenograft tumour growth and metastasis in vivo. Mechanistically, ABCA8 inhibited CRC cell proliferation and metastasis through the Wnt/β-catenin signalling pathway, both in vitro and in vivo. ConclusionWe verified that ABCA8 inhibits the malignant progression of CRC through the Wnt/β-catenin pathway. This newly discovered ABCA8-Wnt-β-catenin signalling axis is probably helpful in guiding the clinical diagnosis and treatment of CRC.