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Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness
in colorectal cancer via EGFR/Akt pathway
#MMPMID29499765
Hu X
; Li YQ
; Li QG
; Ma YL
; Peng JJ
; Cai SJ
J Exp Clin Cancer Res
2018[Mar]; 37
(1
): 41
PMID29499765
show ga
BACKGROUND: Many types of cancers are devoid of the small leucine-rich
proteoglycans: osteoglycin (OGN), but its role in tumorigenesis is poorly studied
especially in colorectal cancers (CRC). Here we aim to evaluate the relationship
between OGN expression patterns and the clinical course of CRC, and the role of
OGN in cancer progression. METHODS: The tissue microarray staining was performed
and the relevance between OGN expression and oncologic outcomes was performed
using Cox regression analysis. The effect of OGN on cell proliferation and
tumorigenesis was examined in vitro and in vivo. Immunoprecipitation assay,
immunofluorescence analysis and internalization assay were used for mechanistic
study. RESULTS: Patients with high expression of OGN were associated with a
profound longer survival in CRC and the high serum OGN level was also indicative
of fewer recurrences consistently. In colon cancer cells, OGN increased
dimerization of EGFR, then triggered EGFR endocytosis and induced the recruitment
of downstream components of the EGFR internalization machinery (Eps15 and
epsin1). Above all, OGN reduced Zeb-1 expression via EGFR/Akt leading to
inhibition of epithelial-mesenchymal transition. As results, in vitro and in
vivo, the OGN expression was demonstrated to reduce cell proliferation, inhibit
invasion of colon cancer cells then impede cancer progression. CONCLUSIONS: There
is a positive association between OGN level and prolonged survival in CRC. OGN
plays a restrictive role in colorectal cancer progression by reduced activation
of EGFR/AKT/Zeb-1.
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