Investigating Chaperonin-Containing TCP-1 subunit 2 as an essential component of the chaperonin complex for tumorigenesis.
Animals
Breast Neoplasms
/ genetics
Carcinogenesis
/ genetics
Cell Line, Tumor
Cell Proliferation
Chaperonin Containing TCP-1
/ genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Mice, Inbred C57BL
Triple Negative Breast Neoplasms
/ genetics
Xenograft Model Antitumor Assays
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 01 2020
21 01 2020
Historique:
received:
10
07
2019
accepted:
03
01
2020
entrez:
23
1
2020
pubmed:
23
1
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Chaperonin-containing TCP-1 (CCT or TRiC) is a multi-subunit complex that folds many of the proteins essential for cancer development. CCT is expressed in diverse cancers and could be an ideal therapeutic target if not for the fact that the complex is encoded by eight distinct genes, complicating the development of inhibitors. Few definitive studies addressed the role of specific subunits in promoting the chaperonin's function in cancer. To this end, we investigated the activity of CCT2 (CCTβ) by overexpressing or depleting the subunit in breast epithelial and breast cancer cells. We found that increasing total CCT2 in cells by 1.3-1.8-fold using a lentiviral system, also caused CCT3, CCT4, and CCT5 levels to increase. Likewise, silencing cct2 gene expression by ~50% caused other CCT subunits to decrease. Cells expressing CCT2 were more invasive and had a higher proliferative index. CCT2 depletion in a syngeneic murine model of triple negative breast cancer (TNBC) prevented tumor growth. These results indicate that the CCT2 subunit is integral to the activity of the chaperonin and is needed for tumorigenesis. Hence CCT2 could be a viable target for therapeutic development in breast and other cancers.
Identifiants
pubmed: 31964905
doi: 10.1038/s41598-020-57602-w
pii: 10.1038/s41598-020-57602-w
pmc: PMC6972895
doi:
Substances chimiques
CCT2 protein, human
0
Chaperonin Containing TCP-1
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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