Abstract
Previous studies revealed that Asporin (ASPN) is a potential mediator in the development of various types of cancer as a secreted stroma protein, but the function of ASPN inside the cancer cells remains largely unknown. Here, we demonstrated a higher expression level of ASPN in colorectal cancer (CRC) than matched normal tissues, and 25% (2/8) CRC showed copy number variation (CNV) gain/amplification in ASPN gene. Both higher ASPN expression levels and ASPN CNV gain/amplification indicated a worse prognosis in CRC patients. ASPN can promote proliferation, migration, and invasion of CRC cells, and inhibit apoptosis by activating Akt/Erk and TGF-β/Smad2/3 signalings. Further investigations revealed that ASPN interacts with Smad2/3, facilitates its translocation into nucleus, and up-regulates the expression of Epithelial-mesenchymal transition (EMT) related genes. Rescue assays confirmed that TGF-β signaling is essential for the effects of ASPN on promoting CRC cell migration and invasion. In conclusion, ASPN promotes the migration and invasion of CRC cells via TGF-β/Smad2/3 pathway and could serve as a potential prognostic biomarker in CRC patients.
Highlights
Colorectal cancer (CRC) is the third leading cancer diagnosed worldwide, with the death rate ranking fourth[1]
ASPN level in colorectal normal tissues was significantly lower than CRC of all four different clinical stages, no difference was revealed among the four CRC subgroups (Fig. 1c)
To further confirm ASPN is overexpressed in CRC, we extracted data from two independent Gene Expression Omnibus (GEO) datasets[26,27], which verified the overexpression of ASPN in CRC at mRNA level (Fig. 1d, e)
Summary
Colorectal cancer (CRC) is the third leading cancer diagnosed worldwide, with the death rate ranking fourth[1]. Even though colonoscopy has been widely used in cancer screening and leads to a decreasing trend in CRC mortality, it remains the main cancer burden in developed countries[1]. Along with the economic-social transformation of many developing countries, CRC incidence of those areas has increased significantly during the past 20 years[2]. ASPN has emerged as a potential biomarker for various types of cancer. Overexpression of ASPN has been identified in breast[13,14,15], prostate[16,17], gastric[18,19], and pancreas[20,21] cancers
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