Summary of project PR001299
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 PR001299. The data can be accessed directly via it's Project DOI: 10.21228/M8T13T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001299 |
| Project DOI: | doi: 10.21228/M8T13T |
| Project Title: | Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance |
| Project Summary: | Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced endoplasmic reticulum-mitochondria contacts (ERMCs) in therapy resistant cells, and genetically or biochemically reducing ERMCs in therapy sensitive tumors phenocopied resistance. ERMCs serve as platforms to transfer Ca2+ and bioactive lipids to mitochondria. Reduced Ca2+ transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ERMCs as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug resistance. |
| Institute: | Columbia University - Medical Center |
| Department: | Neurology |
| Laboratory: | Area-Gomez Lab |
| Last Name: | Yun |
| First Name: | Taekyung |
| Address: | 650 W 168th Street, New York, NY, 10032, USA |
| Email: | tdy2102@cumc.columbia.edu |
| Phone: | 212-305-3836 |
Summary of all studies in project PR001299
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002054 | Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance | Homo sapiens | Columbia University | MS | 2022-01-17 | 1 | 28 | Uploaded data (90.7G)* |
