Abstract
Tumor necrosis factor receptor-associated protein 1 (TRAP1) is abnormally expressed in many cancers. In this study, we showed that TRAP1 is aberrantly upregulated in breast tumors compared to control tissues. TRAP1 knockdown downregulates mitochondrial aerobic respiratory, sensitizes cells to lethal stimuli, and inhibited tumor growth in MDA-MB-231 and MCF-7 breast cancer cells in vivo. TRAP1 overexpression, however, enhances the capacity to cope with stress conditions. These evidences suggested that TRAP1 is required for tumorigenesis. We also found that TRAP1 regulates the mitochondrial morphology. Relatively lower TRAP1 levels are associated with the rod-shaped mitochondrial phenotype in invasive and metastatic MDA-MB-231 breast cancer cells; on the contrary, higher TRAP1 levels are associated with the tubular network-shaped mitochondrial phenotype in non-invasive MCF-7 cells. Interestingly, the expression of TRAP1 in human breast cancer specimens inversely correlates with tumor grade. Overexpression of TRAP1 in MDA-MB-231 cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis of breast cancer and suggested that TRAP1 may therefore be a potential target for breast cancer drug development.
| Original language | English |
|---|---|
| Pages (from-to) | 44495-44508 |
| Number of pages | 14 |
| Journal | Oncotarget |
| Volume | 6 |
| Issue number | 42 |
| DOIs | |
| State | Published - 2015 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Oncology
Cite this
Aberrantly upregulated trap1 is required for tumorigenesis of breast cancer. / Zhang, Bo; Wang, Jing; Huang, Zhen; Wei, Peng; Liu, Ying; Hao, Junfeng; Zhao, Lijing; Zhang, Fenglin; Tu, Yaping; Wei, Taotao.
In: Oncotarget, Vol. 6, No. 42, 2015, p. 44495-44508.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aberrantly upregulated trap1 is required for tumorigenesis of breast cancer
AU - Zhang, Bo
AU - Wang, Jing
AU - Huang, Zhen
AU - Wei, Peng
AU - Liu, Ying
AU - Hao, Junfeng
AU - Zhao, Lijing
AU - Zhang, Fenglin
AU - Tu, Yaping
AU - Wei, Taotao
PY - 2015
Y1 - 2015
N2 - Tumor necrosis factor receptor-associated protein 1 (TRAP1) is abnormally expressed in many cancers. In this study, we showed that TRAP1 is aberrantly upregulated in breast tumors compared to control tissues. TRAP1 knockdown downregulates mitochondrial aerobic respiratory, sensitizes cells to lethal stimuli, and inhibited tumor growth in MDA-MB-231 and MCF-7 breast cancer cells in vivo. TRAP1 overexpression, however, enhances the capacity to cope with stress conditions. These evidences suggested that TRAP1 is required for tumorigenesis. We also found that TRAP1 regulates the mitochondrial morphology. Relatively lower TRAP1 levels are associated with the rod-shaped mitochondrial phenotype in invasive and metastatic MDA-MB-231 breast cancer cells; on the contrary, higher TRAP1 levels are associated with the tubular network-shaped mitochondrial phenotype in non-invasive MCF-7 cells. Interestingly, the expression of TRAP1 in human breast cancer specimens inversely correlates with tumor grade. Overexpression of TRAP1 in MDA-MB-231 cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis of breast cancer and suggested that TRAP1 may therefore be a potential target for breast cancer drug development.
AB - Tumor necrosis factor receptor-associated protein 1 (TRAP1) is abnormally expressed in many cancers. In this study, we showed that TRAP1 is aberrantly upregulated in breast tumors compared to control tissues. TRAP1 knockdown downregulates mitochondrial aerobic respiratory, sensitizes cells to lethal stimuli, and inhibited tumor growth in MDA-MB-231 and MCF-7 breast cancer cells in vivo. TRAP1 overexpression, however, enhances the capacity to cope with stress conditions. These evidences suggested that TRAP1 is required for tumorigenesis. We also found that TRAP1 regulates the mitochondrial morphology. Relatively lower TRAP1 levels are associated with the rod-shaped mitochondrial phenotype in invasive and metastatic MDA-MB-231 breast cancer cells; on the contrary, higher TRAP1 levels are associated with the tubular network-shaped mitochondrial phenotype in non-invasive MCF-7 cells. Interestingly, the expression of TRAP1 in human breast cancer specimens inversely correlates with tumor grade. Overexpression of TRAP1 in MDA-MB-231 cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis of breast cancer and suggested that TRAP1 may therefore be a potential target for breast cancer drug development.
UR - http://www.scopus.com/inward/record.url?scp=84953377802&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84953377802&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6252
DO - 10.18632/oncotarget.6252
M3 - Article
C2 - 26517089
AN - SCOPUS:84953377802
VL - 6
SP - 44495
EP - 44508
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 42
ER -