MTA 1 drives malignant progression and bone metastasis in prostate cancer
Prostate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis‐associated protein 1 ( MTA 1) is highly overexpressed in metastatic tumors and bone metastatic lesions, its exact role in the development of metastasis is unknown. Here, we report the role of MTA 1 i...
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Published in | Molecular oncology Vol. 12; no. 9; pp. 1596 - 1607 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
John Wiley & Sons, Inc
01.09.2018
|
Subjects | |
Online Access | Get full text |
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Summary: | Prostate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis‐associated protein 1 (
MTA
1) is highly overexpressed in metastatic tumors and bone metastatic lesions, its exact role in the development of metastasis is unknown. Here, we report the role of
MTA
1 in prostate cancer progression and bone metastasis
in vitro
and
in vivo
. We found that
MTA
1 silencing diminished formation of bone metastases and impaired tumor growth in intracardiac and subcutaneous prostate cancer xenografts, respectively. This was attributed to reduced colony formation, invasion, and migration capabilities of
MTA
1 knockdown cells. Mechanistic studies revealed that
MTA
1 silencing led to a significant decrease in the expression of cathepsin B (
CTSB
), a cysteine protease critical for bone metastasis, with an expected increase in the levels of E‐cadherin in both cells and xenograft tumors. Moreover, meta‐analysis of clinical samples indicated a positive correlation between
MTA
1 and
CTSB
. Together, these results demonstrate the critical role of
MTA
1 as an upstream regulator of
CTSB
‐mediated events associated with cell invasiveness and raise the possibility that targeting
MTA
1/
CTSB
signaling in the tumor may prevent the development of bone metastasis in prostate cancer. |
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ISSN: | 1574-7891 1878-0261 |
DOI: | 10.1002/1878-0261.12360 |