Dual mechanisms of LYN kinase dysregulation drive aggressive behaviour in breast cancer cells

Tornillo, Giusy, Knowlson, Catherine, Kendrick, Howard, Cooke, Joe, Mirza, Hasan, Aurrekoetxea-Rodriguez, Iskander, d.M. Vivanco, Maria, Buckley, Niamh E., Grigoriadis, Anita and Smalley, Matthew J. ORCID: https://orcid.org/0000-0001-9540-1146 2018. Dual mechanisms of LYN kinase dysregulation drive aggressive behaviour in breast cancer cells. Cell Reports 25 (13) , pp. 3674-3692. 10.1016/j.celrep.2018.11.103

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (6MB) | Preview

Abstract

The SRC-family kinase LYN is highly expressed in triple-negative/basal-like breast cancer (TNBC) and in the cell of origin of these tumors, c-KIT-positive luminal progenitors. Here, we demonstrate LYN is a downstream effector of c-KIT in normal mammary cells and protective of apoptosis upon genotoxic stress. LYN activity is modulated by PIN1, a prolyl isomerase, and in BRCA1 mutant TNBC PIN1 upregulation activates LYN independently of c-KIT. Furthermore, the full-length LYN splice isoform (as opposed to the Δaa25–45 variant) drives migration and invasion of aggressive TNBC cells, while the ratio of splice variants is informative for breast cancer-specific survival across all breast cancers. Thus, dual mechanisms—uncoupling from upstream signals and splice isoform ratios—drive the activity of LYN in aggressive breast cancers.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Additional Information:	This is an open access article under the terms of the CC-BY Attribution 4.0 International license.
Publisher:	Elsevier
ISSN:	2211-1247
Funders:	Cancer Research UK
Date of First Compliant Deposit:	21 November 2018
Date of Acceptance:	29 November 2018
Last Modified:	04 May 2023 05:55
URI:	https://orca.cardiff.ac.uk/id/eprint/116972

Citation Data

Cited 27 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item