Amplification of TLK2 Induces Genomic Instability via Impairing the G2-M Checkpoint.

ABSTRACT: Managing aggressive breast cancers with enhanced chromosomal instability (CIN) is a significant challenge in clinics. Previously, we described that a cell cycle-associated kinase called Tousled-like kinase 2 (TLK2) is frequently deregulated by genomic amplifications in aggressive estrogen receptor-positive (ER⁺) breast cancers. In this study, it was discovered that TLK2 amplification and overexpression mechanistically impair Chk1/2-induced DNA damage checkpoint signaling, leading to a G₂-M checkpoint defect, delayed DNA repair process, and increased CIN. In addition, TLK2 overexpression modestly sensitizes breast cancer cells to DNA-damaging agents, such as irradiation or doxorubicin. To our knowledge, this is the first report linking TLK2 function to CIN, in contrast

SUBMITTER: Kim JA 

PROVIDER: S-EPMC5065758 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature