Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer

被引：60
作者：
Li, Hengcun [1 ]
Zhang, Zheng [1 ]
Chen, Lei [1 ]
Sun, Xiujing [1 ]
Zhao, Yu [1 ]
Guo, Qingdong [1 ]
Zhu, Shengtao [1 ]
Li, Peng [1 ]
Min, Li [1 ]
Zhang, Shutian [1 ]
机构：
[1] Capital Med Univ, Beijing Friendship Hosp, Dept Gastroenterol,Beijing Key Lab Precancerous L, Beijing Digest Dis Ctr,Natl Clin Res Ctr Digest D, Beijing 100050, Peoples R China
来源：
CELL DEATH & DISEASE | 2019年 / 10卷 / 2期
基金：
中国国家自然科学基金;
关键词：
TGF-BETA; GASTRIC-CANCER; INVASION; PROTEIN; GROWTH; SUSCEPTIBILITY; IDENTIFICATION; MECHANISMS; GENE; ASPN;
D O I：
10.1038/s41419-019-1376-9
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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-beta/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-beta 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-beta/Smad2/3 pathway and could serve as a potential prognostic biomarker in CRC patients.
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页数：14
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