In:
The Journal of Pathology, Wiley, Vol. 236, No. 4 ( 2015-08), p. 467-478
Abstract:
Semaphorin‐ 3F ( SEMA3F ), an axonal repulsant in nerve development, has been shown to inhibit the progression of human colorectal cancer ( CRC ); however, the underlying mechanism remains elusive. In this study we found a negative correlation between the levels of SEMA3F and CXCR4 in CRC specimens from 85 patients, confirmed by bioinformatics analysis of gene expression in 229 CRC samples from the Cancer Genome Atlas. SEMA3F high / CXCR4 low patients showed the lowest frequency of lymph node and distant metastasis and the longest survival. Mechanistically, SEMA3F inhibited the invasion and metastasis of CRC cells through PI3K–AKT ‐dependent down‐regulation of the ASCL2–CXCR4 axis. Specifically, ASCL2 enhanced the invasion and metastasis of CRC cells in vitro and expression of ASCL2 correlated with distant metastasis, tumour size and poor overall survival in CRC patients. Treatment of CRC cells with the CXCR4 antagonist AMD3100 attenuated SEMA3F knockdown‐induced invasion and metastasis of CRC cells in vitro and in vivo . Our study thus demonstrates that SEMA3F functions as a suppressor of CRC metastasis via down‐regulating the ASCL2–CXCR4 axis. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Type of Medium:
Online Resource
ISSN:
0022-3417
,
1096-9896
DOI:
10.1002/path.2015.236.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
3119-7
detail.hit.zdb_id:
1475280-3