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 inMolecular oncology Vol. 12; no. 9; pp. 1596 - 1607
Main Authors Kumar, Avinash, Dhar, Swati, Campanelli, Gisella, Butt, Nasir A., Schallheim, Jason M., Gomez, Christian R., Levenson, Anait S.
Format Journal Article
LanguageEnglish
Published Hoboken John Wiley & Sons, Inc 01.09.2018
Subjects
Bone cancer
Bone growth
Bone tumors
Cathepsin B
Cell adhesion & migration
Cell culture
Cysteine proteinase
Genomes
Invasiveness
Kinases
Laboratories
Life sciences
Metastases
Metastasis
Morbidity
Prostate cancer
Proteins
Tumors
Wound healing
Xenografts
United States > US
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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.
ISSN:1574-7891
1878-0261
DOI:10.1002/1878-0261.12360