Summary of project PR002029
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 PR002029. The data can be accessed directly via it's Project DOI: 10.21228/M8BJ9X This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002029 |
| Project DOI: | doi: 10.21228/M8BJ9X |
| Project Title: | FDX2-KO induces global down-regulation of iron-sulfur cluster-containing proteins and senescence-like growth arrest or death in ovarian cancer cells |
| Project Summary: | Recent studies report molecular mechanisms underlying iron-sulfur cluster (Fe-S) biosynthesis and suggest its importance in health and disease. However, a role for Fe-S biosynthesis in cancer contexts remains unclear. Here we report that FDX2, an Fe-S assembly factor, is indispensable for maintenance of cellular Fe-S-containing proteins (Fe-S protein(s)) and proliferation of ovarian cancer (OVC) cells. CRISPR-screening of all metabolism-related genes in OVC cells identified several Fe-S assembly genes as essential for OVC growth. Using an inducible FDX2-KO OVC line, we found that FDX2 loss promotes either senescence-like growth arrest or cell death, depending on TP53 status. Mechanistically, FDX2-loss caused global but differential post transcriptional down-regulation of Fe-S proteins, in turn perturbing respiration, iron-regulation and redox homeostasis, all associated with DNA damage. These results demonstrate significant roles for Fe-S biosynthesis in OVC proliferation and survival and provide information about how the cellular Fe-S-protein network responds to disruptions in Fe-S assembly. |
| Institute: | Tohoku University |
| Department: | Graduate School of Medicine |
| Laboratory: | Department of Biochemical Oncology |
| Last Name: | Tanuma |
| First Name: | Nobu-hiro |
| Address: | 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan |
| Email: | nobuhiro.tanuma.c7@tohoku.ac.jp |
| Phone: | +81-22-381-1165 |
| Publications: | https://doi.org/10.1016/j.jbc.2024.107678, https://www.jbc.org/article/S0021-9258(24)02179-3/fulltext, https://pubmed.ncbi.nlm.nih.gov/39151727/ |
Summary of all studies in project PR002029
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003267 | FDX2-KO induces global down-regulation of iron-sulfur cluster-containing proteins and senescence-like growth arrest or death in ovarian cancer cells | Homo sapiens | Tohoku University | MS | 2024-08-12 | 1 | 8 | Uploaded data (11.4G)* |
