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Unique cartilage matrix-associated protein inhibits the migratory and invasive potential of triple-negative breast cancer.

Abstract：

:Triple-negative breast cancer (TNBC) that lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is a breast cancer subtype with very aggressive metastasis and poor prognosis. Unique cartilage matrix-associated protein (UCMA) is a vitamin K-dependent protein (VKDP) with a high-density γ-carboxyglutamic acid (Gla) domain due to the action of vitamin K. UCMA promotes osteoblast differentiation and mineral deposition in bone and suppresses calcification in vessels. However, correlation between UCMA and TNBC is unknown. This study investigated the inhibitory effect of UCMA on TNBC cell in vitro migration, invasion, and colony formation in addition to in vivo tumorigenesis. Cell migration and invasion significantly decreased in Ucma-overexpressing MDA-MB-231 and 4T1 cells compared to the mock control cells. Also, colony formation and the number of colonies significantly decreased in Ucma-overexpressing MDA-MB-231 and 4T1 cells. These results indicate that UCMA significantly inhibits the migration, invasion, and colony formation of TNBC cells. In an in vivo xenograft mouse model, tumor growth significantly decreased in mice bearing Ucma-overexpressing TNBC cells compared to the mock control cells, indicating that UCMA reduced in vivo tumor growth, similar to the inhibitory role of UCMA in vitro. Survival analysis using publicly available database showed that high UCMA expression significantly correlated with favorable relapse-free survival in TNBC patients compared to those with the other VKDPs, matrix Gla protein (MGP) and osteocalcin (OCN). Collectively, this study suggests that UCMA is a promising new therapeutic agent for TNBC.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Lee SH,Lee YJ,Park SI,Kim JE

doi

10.1016/j.bbrc.2020.07.114

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

680-685

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)31511-4

journal_volume

530

pub_type

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Unique cartilage matrix-associated protein inhibits the migratory and invasive potential of triple-negative breast cancer.