Genetic disruption of calpain-1 and calpain-2 attenuates tumorigenesis in mouse models of HER2+ breast cancer and sensitizes cancer cells to doxorubicin and lapatinib.

ABSTRACT: Calpains are a family of calcium activated cysteine proteases which participate in a wide range of cellular functions including migration, invasion, autophagy, programmed cell death, and gene expression. Calpain-1 and calpain-2 isoforms are ubiquitously expressed heterodimers composed of isoform specific catalytic subunits coupled with an obligate common regulatory subunit encoded by capns1. Here, we report that conditional deletion of capns1 disrupted calpain-1 and calpain-2 expression and activity, and this was associated with delayed tumorigenesis and altered signaling in a transgenic mouse model of spontaneous HER2⁺ breast cancer and effectively blocked tumorigenesis in an orthotopic engraftment model. Furthermore, capns1 knockout in a tumor derived cell line c

SUBMITTER: MacLeod JA 

PROVIDER: S-EPMC6161787 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature