Cx43 phosphorylation sites regulate pancreatic cancer metastasis.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is aggressive, highly metastatic and characterized by a robust desmoplasia. Connexin proteins that form gap junctions have been implicated in tumor suppression for over 30 years. Cx43, the most widely expressed connexin, regulates cell behaviors, including migration and proliferation. Thus, we hypothesized that Cx43 could regulate PDA progression. Phosphorylation of Cx43 by Casein Kinase 1 (CK1) regulates gap junction assembly. We interbred the well-established Kras^{LSL-G12D/+;p48Cre/+} (KC) mouse model of PDA with homozygous "knock-in" mutant Cx43 mice bearing amino acid substitution at CK1 sites (Cx43^CK1A) and found profound and surprising effects on cancer progression. Crossing the Cx43^CK1A mouse onto the KC backgroun

SUBMITTER: Solan JL 

PROVIDER: S-EPMC8191514 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature