Summary of project PR002476
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002476. The data can be accessed directly via it's Project DOI: 10.21228/M8KV7F This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002476 |
| Project DOI: | doi: 10.21228/M8KV7F |
| Project Title: | Targeting ESRP1 inhibits the assembly of respiratory chain supercomplexes to overcome ferroptosis-resistance in gastric cancer |
| Project Summary: | Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of ESRP1/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of ESRP1. We show that ESRP1 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting ESRP1 and promoting TRIM25-mediated ubiquitination and degradation of ESRP1. Here we show, ESRP1/SCAF1 are important in ferroptosis-resistance, and targeting ESRP1 with zanamivir has therapeutic potential. We conducted untargeted metabolomic analysis of Erastin-resis SNU-668 cells transfected with shRNA-ESRP1 or shRNA-NC. |
| Institute: | Fudan University Shanghai Cancer Center |
| Department: | Department of Gastric Surgery |
| Last Name: | Mingzhe |
| First Name: | Ma |
| Address: | building 18, 29 Nong Linling Road, Xuhui district, Shanghai, 200024, China |
| Email: | mmz666@163.com, ding@bioinformatics.com.cn |
| Phone: | 13917006049 |
Summary of all studies in project PR002476
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003953 | Metabolomic Profiling of Gastric Cancer Post-ESRP1 Gene Knockout | Homo sapiens | Fudan University Shanghai Cancer Center | MS* | 2025-06-11 | 1 | 12 | Uploaded data (1.8G)* |
