Calcium Influx Caused by ER Stress Inducers Enhances Oncolytic Adenovirus Enadenotucirev Replication and Killing through PKCα Activation.

ABSTRACT: Oncolytic viruses represent an emerging approach to cancer therapy. However, better understanding of their interaction with the host cancer cell and approaches to enhance their efficacy are needed. Here, we investigate the effect of chemically induced endoplasmic reticulum (ER) stress on the activity of the chimeric group B adenovirus Enadenotucirev, its closely related parental virus Ad11p, and the archetypal group C oncolytic adenovirus Ad5. We show that treatment of colorectal and ovarian cancer cell lines with thapsigargin or ionomycin caused an influx of Ca2+, leading to an upregulation in E1A transcript and protein levels. Increased E1A protein levels, in turn, increased levels of expression of the E2B viral DNA polymerase, genome replication, late viral protein expression, infectiou

SUBMITTER: Taverner WK 

PROVIDER: S-EPMC6931121 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature