Inactivation of HIPK2 attenuates KRAS^G12D activity and prevents pancreatic tumorigenesis.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) features KRAS mutations in approximately 90% of human cases and excessive stromal response, termed desmoplastic reaction. Oncogenic KRAS drives pancreatic carcinogenesis by acting on both epithelial cells and tumor microenvironment (TME). We have previously shown that Homeodomain-Interacting Protein Kinase 2 (HIPK2) cooperates with KRAS in sustaining ERK1/2 phosphorylation in human colorectal cancers. Here, we investigated whether HIPK2 contributes to oncogenic KRAS-driven tumorigenesis in vivo, in the onset of pancreatic cancer.

Methods

We employed an extensively characterized model of KRAS^G12D-dependent preinvasive PDAC, the Pdx1-Cre;LSL-KRas^G12D/+ (KC) mice. In these mice, HIPK2 was inhibited by gene

SUBMITTER: Sozzi S 

PROVIDER: S-EPMC11437985 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature