Transgenic Expression of the Mitochondrial Chaperone TNFR-associated Protein 1 (TRAP1) Accelerates Prostate Cancer Development
(2016) In Journal of Biological Chemistry 291(48). p.25247-25254- Abstract
Protein homeostasis, or proteostasis, is required for mitochondrial function, but its role in cancer is controversial. Here we show that transgenic mice expressing the mitochondrial chaperone TNFR-associated protein 1 (TRAP1) in the prostate develop epithelial hyperplasia and cellular atypia. When examined on a Pten(+/-) background, a common alteration in human prostate cancer, TRAP1 transgenic mice showed accelerated incidence of invasive prostatic adenocarcinoma, characterized by increased cell proliferation and reduced apoptosis, in situ Conversely, homozygous deletion of TRAP1 delays prostatic tumorigenesis in Pten(+/-) mice without affecting hyperplasia or prostatic intraepithelial neoplasia. Global profiling of Pten(+/-)-TRAP1... (More)
Protein homeostasis, or proteostasis, is required for mitochondrial function, but its role in cancer is controversial. Here we show that transgenic mice expressing the mitochondrial chaperone TNFR-associated protein 1 (TRAP1) in the prostate develop epithelial hyperplasia and cellular atypia. When examined on a Pten(+/-) background, a common alteration in human prostate cancer, TRAP1 transgenic mice showed accelerated incidence of invasive prostatic adenocarcinoma, characterized by increased cell proliferation and reduced apoptosis, in situ Conversely, homozygous deletion of TRAP1 delays prostatic tumorigenesis in Pten(+/-) mice without affecting hyperplasia or prostatic intraepithelial neoplasia. Global profiling of Pten(+/-)-TRAP1 transgenic mice by RNA sequencing and reverse phase protein array reveals modulation of oncogenic networks of cell proliferation, apoptosis, cell motility, and DNA damage. Mechanistically, reconstitution of Pten(+/-) prostatic epithelial cells with TRAP1 increases cell proliferation, reduces apoptosis, and promotes cell invasion without changes in mitochondrial bioenergetics. Therefore, TRAP1 is a driver of prostate cancer in vivo and an "actionable" therapeutic target.
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- author
- Lisanti, Sofia ; Garlick, David S ; Bryant, Kelly G ; Tavecchio, Michele LU ; Mills, Gordon B. ; Lu, Yiling ; Kossenkov, Andrew V ; Showe, Louise C ; Languino, Lucia R and Altieri, Dario C
- publishing date
- 2016-11-25
- type
- Contribution to journal
- publication status
- published
- in
- Journal of Biological Chemistry
- volume
- 291
- issue
- 48
- pages
- 8 pages
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- scopus:84997585147
- pmid:27754870
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M116.745950
- language
- English
- LU publication?
- no
- id
- 8ab372ab-5135-475e-859d-58a1a1d755d2
- date added to LUP
- 2017-03-07 09:02:31
- date last changed
- 2024-03-31 05:30:50
@article{8ab372ab-5135-475e-859d-58a1a1d755d2,
abstract = {{<p>Protein homeostasis, or proteostasis, is required for mitochondrial function, but its role in cancer is controversial. Here we show that transgenic mice expressing the mitochondrial chaperone TNFR-associated protein 1 (TRAP1) in the prostate develop epithelial hyperplasia and cellular atypia. When examined on a Pten(+/-) background, a common alteration in human prostate cancer, TRAP1 transgenic mice showed accelerated incidence of invasive prostatic adenocarcinoma, characterized by increased cell proliferation and reduced apoptosis, in situ Conversely, homozygous deletion of TRAP1 delays prostatic tumorigenesis in Pten(+/-) mice without affecting hyperplasia or prostatic intraepithelial neoplasia. Global profiling of Pten(+/-)-TRAP1 transgenic mice by RNA sequencing and reverse phase protein array reveals modulation of oncogenic networks of cell proliferation, apoptosis, cell motility, and DNA damage. Mechanistically, reconstitution of Pten(+/-) prostatic epithelial cells with TRAP1 increases cell proliferation, reduces apoptosis, and promotes cell invasion without changes in mitochondrial bioenergetics. Therefore, TRAP1 is a driver of prostate cancer in vivo and an "actionable" therapeutic target.</p>}},
author = {{Lisanti, Sofia and Garlick, David S and Bryant, Kelly G and Tavecchio, Michele and Mills, Gordon B. and Lu, Yiling and Kossenkov, Andrew V and Showe, Louise C and Languino, Lucia R and Altieri, Dario C}},
issn = {{1083-351X}},
language = {{eng}},
month = {{11}},
number = {{48}},
pages = {{25247--25254}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Transgenic Expression of the Mitochondrial Chaperone TNFR-associated Protein 1 (TRAP1) Accelerates Prostate Cancer Development}},
url = {{http://dx.doi.org/10.1074/jbc.M116.745950}},
doi = {{10.1074/jbc.M116.745950}},
volume = {{291}},
year = {{2016}},
}