Skip to main content
Przejdź do strony domowej Komisji Europejskiej (odnośnik otworzy się w nowym oknie)
polski pl
CORDIS - Wyniki badań wspieranych przez UE
CORDIS
Zawartość zarchiwizowana w dniu 2024-06-18

Dynamic regulation of Ras signaling – a novel way to attenuate PI3K activity in cancer and inflammation

Cel

Ras genes take a center stage in signal transduction and molecular oncology, where Ras-driven signaling pathways control proliferation, differentiation, cell adhesion, apoptosis, and cell migration. Mutations in RAS are very common in cancer, and have been found in 20-30% of all human tumors. Moreover, constitutive Ras activation is known to trigger senescence in the absence of “second hit” mutations (e.g. loss of p53). Interestingly, both processes - cancer progression and oncogene-induced cellular senescence - were shown to be dependent on Ras interaction with phosphoinositide 3-kinase (PI3K), which points to a dominant role of Ras-mediated PI3K activation in proliferative disease.
Here we propose to investigate the possibility that Ras/PI3K interactions are dynamically regulated, which is supported by preliminary data: in certain cellular states, post-translational modification of Ras disrupts its binding to PI3K.
We aim to elucidate the importance of this process in physiology and disease. We assume that regulated Ras interactions with PI3Kalpha act in cancer progression, while Ras/PI3Kgamma complexes transiently regulate inflammatory processes. Along these lines, we aim to uncover cellular signaling networks that dynamically dissociate Ras from PI3K. When the above mechanism is validated, we plan to study the consequences of the abrogation of Ras/PI3K interactions in “in vivo” mouse models. These will elucidate if and how PI3K detachment from Ras acts as a a general and central mechanism to balance inflammatory cell recruitment, oncogen-mediated metastasis, proliferation and senescence.

Dziedzina nauki (EuroSciVoc)

Program(-y)

Temat(-y)

Zaproszenie do składania wniosków

FP7-PEOPLE-2009-IIF
Zobacz inne projekty w ramach tego zaproszenia

System finansowania

MC-IIF - International Incoming Fellowships (IIF)

Koordynator

UNIVERSITAT BASEL
Wkład UE
€ 172 065,20
Koszt całkowity
Brak danych