Xu, Yichen, Zhang, Hua, Nguyen, Van, Angelopoulos, Nikos, Nunes, Joao, Reid, Alistair, Buluwela, Laki, Magnani, Luca, Stebbing, Justin and Giamas, Georgios (2015) LMTK3 represses tumor suppressor-like genes through chromatin remodeling in breast cancer. Cell Reports, 12 (5). pp. 837-849. ISSN 2211-1247

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Abstract

LMTK3 is an oncogenic receptor tyrosine kinase (RTK) implicated in various types of cancer, including breast, lung, gastric, and colorectal cancer. It is local-ized in different cellular compartments, but its nuclear function has not been investigated so far. We mapped LMTK3 binding across the genome using ChIP-seq and found that LMTK3 binding events are corre-lated with repressive chromatin markers. We further identified KRAB-associated protein 1 (KAP1) as a binding partner of LMTK3. The LMTK3/KAP1 interac-tion is stabilized by PP1a, which suppresses KAP1 phosphorylation specifically at LMTK3-associated chromatin regions, inducing chromatin condensation and resulting in transcriptional repression of LMTK3-bound tumor suppressor-like genes. Furthermore, LMTK3 functions at distal regions in tethering the chromatin to the nuclear periphery, resulting in H3K9me3 modification and gene silencing. In sum-mary, we propose a model where a scaffolding func-tion of nuclear LMTK3 promotes cancer progression through chromatin remodeling.

Item Type:	Article
Keywords:	LMTK3, Tumor Suppressor, Chromatin Remodeling, Breast Cancer
Schools and Departments:	School of Life Sciences > Biochemistry
Depositing User:	Georgios Giamas
Date Deposited:	28 Jul 2015 09:32
Last Modified:	03 Jul 2019 02:35
URI:	http://sro.sussex.ac.uk/id/eprint/55769

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