MTA 1 drives malignant progression and bone metastasis in prostate cancer

Autor: Anait S. Levenson, Nasir A. Butt, Gisella Campanelli, Swati Dhar, Christian R. Gomez, Jason Schallheim, Avinash Kumar
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Cancer Research
cathepsin B
Cell
luciferase imaging
Cathepsin B
Intracardiac injection
Metastasis
Mice
Prostate cancer
0302 clinical medicine
Cell Movement
Research Articles
bone metastasis
Gene knockdown
Bone metastasis
General Medicine
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Cadherins
prostate cancer
Cell Transformation
Neoplastic
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Disease Progression
Heterografts
Molecular Medicine
Signal Transduction
Research Article
Epithelial-Mesenchymal Transition
intracardiac xenografts
Bone Neoplasms
Mice
Transgenic
lcsh:RC254-282
Histone Deacetylases
03 medical and health sciences
Antigens
CD
Cell Line
Tumor
Genetics
medicine
Animals
Humans
Gene silencing
Neoplasm Invasiveness
Gene Silencing
business.industry
Prostatic Neoplasms
medicine.disease
Repressor Proteins
030104 developmental biology
MTA1
Trans-Activators
Cancer research
business
Zdroj: Molecular Oncology
Molecular Oncology, Vol 12, Iss 9, Pp 1596-1607 (2018)
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.12360
Popis: Prostate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis‐associated protein 1 (MTA1) 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 MTA1 in prostate cancer progression and bone metastasis in vitro and in vivo. We found that MTA1 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 MTA1 knockdown cells. Mechanistic studies revealed that MTA1 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 MTA1 and CTSB. Together, these results demonstrate the critical role of MTA1 as an upstream regulator of CTSB‐mediated events associated with cell invasiveness and raise the possibility that targeting MTA1/CTSB signaling in the tumor may prevent the development of bone metastasis in prostate cancer.
Databáze: OpenAIRE
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