Non-canonical role for the ataxia-telangiectasia-Rad3 pathway in STAT3 activation in human multiple myeloma cells.

ABSTRACT:

Purpose

The goal of this study was to characterize the relationship between ATR and STAT3 interactions in human multiple myeloma (MM) cells.

Methods

Various MM cell lines, including IL-6-dependent cells were exposed to ATR inhibitors and effects on STAT3 Tyr705 and Ser727 were monitored by WB analysis and ImageStream analysis. Parallel studies examined induction of cell death, STAT3 DNA binding activity, and expression of STAT3 downstream targets (BCL-X_L, MCL-1, c-MYC). Validation was obtained in ATR shRNA knock-down cells, and in cells ectopically expressing BCL-X_L, MCL-1, or c-MYC. Analogous studies were performed in primary MM cells and in a MM xenograft model.

Results

Multiple pharmacologic ATR inhibitors inhibited STAT3 Tyr705 (but not Ser72

SUBMITTER: Li L 

PROVIDER: S-EPMC10618375 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature