Open AccessMTA 1 drives malignant progression and bone metastasis in prostate cancer
Author(s) -
Kumar Avinash,
Dhar Swati,
Campanelli Gisella,
Butt Nasir A.,
Schallheim Jason M.,
Gomez Christian R.,
Levenson Anait S.
Publication year - 2018
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12360
Subject(s) - prostate cancer , metastasis , cancer research , gene silencing , bone metastasis , medicine , prostate , cancer , gene knockdown , pathology , biology , cell culture , biochemistry , genetics , gene
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.