Lysosomal lipid switch sensitises to nutrient deprivation and mTOR targeting in pancreatic cancer.

ABSTRACT:

Objective

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited therapeutic options. However, metabolic adaptation to the harsh PDAC environment can expose liabilities useful for therapy. Targeting the key metabolic regulator mechanistic target of rapamycin complex 1 (mTORC1) and its downstream pathway shows efficacy only in subsets of patients but gene modifiers maximising response remain to be identified.

Design

Three independent cohorts of PDAC patients were studied to correlate PI3K-C2γ protein abundance with disease outcome. Mechanisms were then studied in mouse (KPC mice) and cellular models of PDAC, in presence or absence of PI3K-C2γ (WT or KO). PI3K-C2γ-dependent metabolic rewiring and its impact on mTORC1 regulation were assessed in condition

SUBMITTER: De Santis MC 

PROVIDER: S-EPMC9872233 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature