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Lysosomes as targets for cancer therapy

Objective

"Knowing that the lysosomes contain a powerful cocktail of hydrolases capable of digesting cells and entire tissues, it is obvious that the maintenance of lysosomal membrane integrity is of utmost importance for all cells, and especially for cancer cells with dramatically increased lysosomal activity. Yet, the mechanisms that regulate lysosomal membrane stability have remained obscure, largely due to the lack of methods sensitive enough to detect partial lysosomal leakage and suitable for screening purposes. We have finally succeeded in developing such a method, which allows me to propose here a project whose major aim is to reveal how cells maintain the integrity of lysosomal membranes. Based on our emerging data that firmly connect heat shock protein 70 and sphingolipid metabolism to lysosomal membrane stability, we will devote a large part of the project to the molecular details of these connections and to the characterization of the effects of new and already approved (cationic amphiphilic drugs) sphingolipid-regulating drugs on lysosomal membrane stability and cell survival. Additionally, we will screen selected siRNA libraries to identify signaling networks and lysosome-associated proteins essential for lysosomal membrane integrity, and small molecule libraries to identify compounds that induce lysosomal cell death. The next step is to identify lysosome-stabilizing mechanisms that are especially important for cancer cell survival. And the ultimate goal is to validate corresponding drug targets and drugs (old and new) for the induction of lysosomal cell death in therapy resistant cancers. As a “by-product” we expect to identify putative drug targets for the treatment of degenerative diseases and lipid storage disorders, where the stabilization of the lysosomal membranes promotes cell survival."

Call for proposal

ERC-2013-ADG
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

KRAEFTENS BEKAEMPELSE
Address
Strandboulevarden 49
2100 Koebenhavn
Denmark
Activity type
Research Organisations
EU contribution
€ 2 499 960
Principal investigator
Marja Helena Jäättelä (Prof.)
Administrative Contact
Claus Skytte Rasmussen (Mr.)

Beneficiaries (1)

KRAEFTENS BEKAEMPELSE
Denmark
EU contribution
€ 2 499 960
Address
Strandboulevarden 49
2100 Koebenhavn
Activity type
Research Organisations
Principal investigator
Marja Helena Jäättelä (Prof.)
Administrative Contact
Claus Skytte Rasmussen (Mr.)