Mitochondrial TSPO Promotes Hepatocellular Carcinoma Progression through Ferroptosis Inhibition and Immune Evasion
Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor prognosis, and novel treatment strategies are urgently needed. Mitochondria are key regulators of cellular homeostasis and potential targets for tumor therapy. Here, the role of mitochondrial translocator protein (TSPO) in the regulation of ferroptosis and antitumor immunity is investigated and the potential therapeutic implications for HCC are assessed. TSPO is highly expressed in HCC and associated with poor prognosis. Gain‐ and loss‐of‐function experiments present that TSPO promotes HCC cell growth, migration, and invasion in vitro and in vivo. In addition, TSPO inhibits ferroptosis in HCC cells via enhancing the Nrf2‐dependent antioxidant defense system. Mechanistically, TSPO directly interacts with P62 and interferes with autophagy, leading to the accumulation of P62. The P62 accumulation competes with KEAP1, preventing it from targeting Nrf2 for proteasomal degradation. Furthermore, TSPO promotes HCC immune escape by upregulating PD‐L1 expression through Nrf2‐mediated transcription. Notably, TSPO inhibitor PK11195 combines with anti‐PD‐1 antibody showing a synergistic anti‐tumor effect in a mouse model. Overall, the results demonstrated that mitochondrial TSPO promotes HCC progression by inhibiting ferroptosis and antitumor immunity. Targeting TSPO can be a promising new strategy for HCC treatment.
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Erschienen in
-
Mitochondrial TSPO Promotes Hepatocellular Carcinoma Progression through Ferroptosis Inhibition and Immune Evasion ; day:30 ; month:03 ; year:2023 ; extent:13
Advanced science ; (30.03.2023) (gesamt 13)
- Urheber
-
Zhang, Deguo
Man, Da
Lu, Jiahua
Jiang, Yifan
Ding, Bo
Su, Rong
Tong, Rongliang
Chen, Junru
Yang, Beng
Zheng, Shusen
Chen, Diyu
Wu, Jian
- DOI
-
10.1002/advs.202206669
- URN
-
urn:nbn:de:101:1-2023033015154644825494
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
14.08.2025, 10:52 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Zhang, Deguo
- Man, Da
- Lu, Jiahua
- Jiang, Yifan
- Ding, Bo
- Su, Rong
- Tong, Rongliang
- Chen, Junru
- Yang, Beng
- Zheng, Shusen
- Chen, Diyu
- Wu, Jian
Ähnliche Objekte (12)
Berechnung zwei- und dreidimensionaler turbulenter Grenzschichten
The first confirmed case of COVID-19 in Tanzania: recommendations based on lesson learned from China
ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
The influence of aftershocks on seismic hazard analysis: A case study from Xichang and the surrounding areas
The influence of aftershocks on seismic hazard analysis: a case study from Xichang and the surrounding areas
Approaches to reduce false positives and false negatives in the analysis of microarray data: applications in type 1 diabetes research
The screening and preliminary construction of quality mutant population for cultivar “Nipponbare” in japonica rice (Oryza sativa)
AR assistance for efficient dynamic target search
Evaluating the effects of land use and cover change on the decrease of surface wind speed over China in recent 30 years using a statistical downscaling method
Efficacy of balance training for hip fracture patients: a meta-analysis of randomized controlled trials
Seismic Hazard Analysis of China’s Mainland Based on a New Seismicity Model
HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma
Berechnung zwei- und dreidimensionaler turbulenter Grenzschichten
The first confirmed case of COVID-19 in Tanzania: recommendations based on lesson learned from China
ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
The influence of aftershocks on seismic hazard analysis: A case study from Xichang and the surrounding areas
The influence of aftershocks on seismic hazard analysis: a case study from Xichang and the surrounding areas
Approaches to reduce false positives and false negatives in the analysis of microarray data: applications in type 1 diabetes research
The screening and preliminary construction of quality mutant population for cultivar “Nipponbare” in japonica rice (Oryza sativa)
AR assistance for efficient dynamic target search
Evaluating the effects of land use and cover change on the decrease of surface wind speed over China in recent 30 years using a statistical downscaling method
Efficacy of balance training for hip fracture patients: a meta-analysis of randomized controlled trials
Seismic Hazard Analysis of China’s Mainland Based on a New Seismicity Model
HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma
Berechnung zwei- und dreidimensionaler turbulenter Grenzschichten
The first confirmed case of COVID-19 in Tanzania: recommendations based on lesson learned from China
ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
The influence of aftershocks on seismic hazard analysis: A case study from Xichang and the surrounding areas
The influence of aftershocks on seismic hazard analysis: a case study from Xichang and the surrounding areas
Approaches to reduce false positives and false negatives in the analysis of microarray data: applications in type 1 diabetes research
The screening and preliminary construction of quality mutant population for cultivar “Nipponbare” in japonica rice (Oryza sativa)
AR assistance for efficient dynamic target search
Evaluating the effects of land use and cover change on the decrease of surface wind speed over China in recent 30 years using a statistical downscaling method
Efficacy of balance training for hip fracture patients: a meta-analysis of randomized controlled trials
Seismic Hazard Analysis of China’s Mainland Based on a New Seismicity Model