The role of LMTK3 in chromatin remodeling and transcriptional regulation

Abstract

Nuclear receptor tyrosine kinases such as EGFR have been shown to be associated with increased tumor grade and poorer patient survival. One explanation for this is that following nuclear transport, these RTKs are directly involved in the transcriptional regulation through chromatin binding. LMTK3 is a novel oncogenic RTK implicated in breast cancer, whose cytoplasmic and nuclear abundance are highly associated with poorer survival in breast cancer patient. So far the function of the cytoplasmic LMTK3 in breast cancer growth, invasion and endocrine resistance has been addressed, however little is known about the role of nuclear LMTK3. In our recent study, we discovered that LMTK3 binds chromatin via its interacting partners PP1? and KAP1. Moreover, LMTK3 induces the tethering of chromatin to the nuclear periphery. These events result in chromatin condensation and subsequent transcriptional repression of various tumor suppressor-like genes, leading to breast cancer progression. Overall, this research work provides an insight of the nuclear kinase function and suggests that targeting LMTK3 may have further clinical potentials in treating breast cancer.