Summary of project PR002255
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 PR002255. The data can be accessed directly via it's Project DOI: 10.21228/M84V7D This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002255 |
| Project DOI: | doi: 10.21228/M84V7D |
| Project Title: | Targeting the c-MYC/ELOVL6 Pathway Alters Cell Membrane Mechanics and Enhances Chemotherapeutic Efficacy in Pancreatic Cancer |
| Project Summary: | Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, marked by a survival rate of only 12%. Consequently, the exploration of novel therapeutic strategies becomes a critical clinical imperative. Among the genetic alterations contributing to PDAC, c-MYC (an oncogenic transcription factor) overexpression arises due to upstream mutations, amplifications, and copy number alterations. c-MYC serves as a key regulator in the tumor's metabolic reprogramming, playing a pivotal role in proliferation, migration, and metastasis. This study delves into the investigation of the role of the elongase ELOVL6 in c-MYC-induced cell transformation and its potential as a therapeutic target in PDAC. Here, we demonstrate that c-MYC regulates lipid elongation to promote cell transformation, offering a new avenue for therapeutic intervention. Initially, we show the direct regulation of ELOVLs expression by c-MYC in various PDAC mouse models and cell lines, elucidating its upregulation during transformation and tumor progression. Genetic or chemical inhibition of ELOVL6 results in decreased proliferation and migration, accompanied by alterations in fatty acid elongation. These changes in fatty acid composition led to modifications in membrane rigidity, permeability, and thickness, which collectively affect micropinocytosis and macropinocytosis. Importantly, we observe an increase in Abraxane uptake and a synergistic effect when combined with ELOVL6 interference in vitro. In vivo validation demonstrates that ELOVL6 inhibition significantly reduces tumor growth and enhances the response to Abraxane, thereby increasing overall survival. Altogether, these results position ELOVL6 as a promising therapeutic target in the treatment of PDAC. |
| Institute: | Universidad Francisco de Vitoria - Hospital 12 de Octubre |
| Last Name: | Sánchez-Arévalo Lobo |
| First Name: | Víctor Javier |
| Address: | Carretera Pozuelo-Majadahonda, km 1,800, Pozuelo de Alarcón, Madrid, 28223, Spain |
| Email: | victor.sanchezarevalo@ufv.es |
| Phone: | +34 91 709 14 00 |
| Publications: | DOI: 10.1101/2024.11.11.622928 |
Summary of all studies in project PR002255
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003645 | Targeting the c-MYC/ELOVL6 Pathway Alters Cell Membrane Mechanics and Enhances Chemotherapeutic Efficacy in Pancreatic Cancer | Homo sapiens | Universidad Francisco de Vitoria - Hospital 12 de Octubre | MS | 2025-01-26 | 1 | 17 | Uploaded data (18M)* |
