PuSH - Publication Server of Helmholtz Zentrum München: A novel AMPK inhibitor sensitizes pancreatic cancer cells to ferroptosis induction.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Schneider, C.* ; Hilbert, J.* ; Genevaux, F.* ; Höfer, S.* ; Kraus, L.* ; Schicktanz, F.* ; Contreras, C.T.* ; Jansari, S.* ; Papargyriou, A. ; Richter, T.* ; Alfayomy, A.M.* ; Falcomatà, C.* ; Schneeweis, C.* ; Orben, F.* ; Öllinger, R.* ; Wegwitz, F.* ; Boshnakovska, A.* ; Rehling, P.* ; Müller, D.* ; Ströbel, P.* ; Ellenrieder, V.* ; Conradi, L.* ; Hessmann, E.* ; Ghadimi, M.* ; Grade, M.* ; Wirth, M.* ; Steiger, K.* ; Rad, R.* ; Kuster, B.* ; Sippl, W.* ; Reichert, M.* ; Saur, D.* ; Schneider, G.*

A novel AMPK inhibitor sensitizes pancreatic cancer cells to ferroptosis induction.

Adv. Sci.:e2307695 (2024)

DOI

PMC

Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

Abstract
Metrics
Extra information

Cancer cells must develop strategies to adapt to the dynamically changing stresses caused by intrinsic or extrinsic processes, or therapeutic agents. Metabolic adaptability is crucial to mitigate such challenges. Considering metabolism as a central node of adaptability, it is focused on an energy sensor, the AMP-activated protein kinase (AMPK). In a subtype of pancreatic ductal adenocarcinoma (PDAC) elevated AMPK expression and phosphorylation is identified. Using drug repurposing that combined screening experiments and chemoproteomic affinity profiling, it is identified and characterized PF-3758309, initially developed as an inhibitor of PAK4, as an AMPK inhibitor. PF-3758309 shows activity in pre-clinical PDAC models, including primary patient-derived organoids. Genetic loss-of-function experiments showed that AMPK limits the induction of ferroptosis, and consequently, PF-3758309 treatment restores the sensitivity toward ferroptosis inducers. The work established a chemical scaffold for the development of specific AMPK-targeting compounds and deciphered the framework for the development of AMPK inhibitor-based combination therapies tailored for PDAC.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Ampk ; Ferroptosis ; Pancreatic Cancer; Activated Protein-kinase; Metastasis; Promotes; Phosphorylation; Pf-3758309; Generation; Resistance; Plasticity; Prediction; Molecules

ISSN (print) / ISBN 2198-3844

e-ISSN 2198-3844

Journal Advanced science

Quellenangaben Article Number: e2307695

Publisher Wiley

Publishing Place Weinheim

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)

Grants DKTK (German Cancer Consortium) Strategic Initiative Organoid Platform