Thrombospondin-1 counteracts the p97 inhibitor CB-5083 in colon carcinoma cells.

ABSTRACT: p97 has recently emerged as a therapeutic target for cancer due to its essential functions in protein homeostasis. CB-5083 is a first-in-class, potent and selective ATP-competitive p97 inhibitor that induces proteotoxic stress in cancer cells. Potential mechanisms regulating the sensitivity of cells to p97 inhibition remain poorly studied. Here, we demonstrate that Thrombospondin-1 (THBS1) is a CB-5083-upregulated gene that helps confer resistance of HCT116 cells to CB-5083. Our immunoblotting and immunofluorescence data showed that CB-5083 significantly increases the steady-state abundance of THBS1. Blockade of THBS1 induction sensitized cells to CB-5083-mediated growth inhibition. Suppression of THBS1 caused an increase of CB-5083-induced sub-G1 population and caspase 3/7 activity sugges

SUBMITTER: Her NG 

PROVIDER: S-EPMC7469669 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature